The Editorial Office and Publisher of the Journal are not responsible for missing matter in the Abstracts

Clinical Protocol for Clinicopathological Conference

Discussant: Bhaskar Nundy; Bengaluru

Pathologist: Kim Vaiphei, Professor, Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Name: Mr.B, Age: 28 years, Sex: Male,

1st admission: DOA: 3.7.2012, DOD: 9.8.2012

2nd admission: DOA: 7.9.2012, DOD: 18.9.2012

3rd admission: DOA: 5.10.2012, DOD: 10.10.2012

4th admission: DOA: 4.1.2013, DO Demise: 15.1.2013

Presenting Complaints: Pain abdomen and vomiting from December 2011, abdominal distension and diarrhea from May 2012.

History of presenting illness: Symptomatic since December 2011 with history of recurrent episodes of colicky pain abdomen associated with vomiting. He was evaluated at a local hospital with contrast-enhanced computed tomography (CECT) abdomen and was started on antitubercular treatment (ATT) in January 2012. He was noncompliant to treatment and was restarted on ATT in April 2012. He progressed to develop abdominal distension and diarrhea along with significant loss of appetite and weight. No history of fever, blood in stools, lump in abdomen. In July 2012 he was referred to PGI, was evaluated for painful small bowel diarrhea with subacute intestinal obstruction (SAIO) and malabsorption and was found to have jejunal stricture which on biopsy revealed an infiltrative disorder (immunoproliferative small intestinal disease or low grade lymphoma). ATT was stopped and started on comparison of a standard regimen (CHOP) regimen (1st dose on 6.8.2012) along with doxycycline. In view of severe malnutrition high protein diet was supplemented and also started on diuretics for anasarca. He improved symptomatically and was discharged. Subsequently he was readmitted on 2 more occasions to receive next cycles of CHOP regimen. In January 2013 he had recurrence of abdominal distension along with pedal edema and worsening diarrhea for he was readmitted and evaluated further.

Past history: No history of similar illness in past. No history of tuberculosis, abdominal surgeries, diabetes, hypertension, drug allergies. Personal history: Chronic alcoholic for 5 years (60 g/day). Chronic smoker with smoking index of 100. Family history: Non-contributory.

Examination

General examination: Emaciated. Height–1.74 m, weight–39 kg, BMI: 10.34 kg/m2 (1st admission), Weight–39 kg, BMI: 15 kg/m2 (last admission) pallor +, pedal edema +, clubbing +, LN + (B/L cervical, axillary, inguinal, 0.5 cm size) icterus -, cyanosis-

Vital data: PR – 65/min, regular, BP – 100/70 mmHg, RR – 18/min, temperature – afebrile.

Abdominal examination: Distended abdomen with ascites. No organomegaly/palpable lump, normal bowel sounds.

Other systems: CVS - normal S1 and S2. No rub. Respiratory system – normal vesicular breath sounds both sides, no crepitation or rub. CNS – normal.

Investigations (All admissions combined)

Work up for diarrhea: Stool examination- No ova or cyst, no atypical organisms, culture- no growth of Salmonella or Shigella, no Clostridium difficile toxin, fat globules-70-80/HPF. D-Xylose test: Suggestive of mucosal malabsorption (0.6 g/5 g/5 hrs urine), anti-tTG antibody-negative, Fat pad FNAC for amyloid- negative, absolute eosinophil count- 40 cells/mm3 (6.7.12), Mantoux test- negative. HIV- negative, HBsAg – negative, anti-HCV – negative.

Ultrasound abdomen (1st admission - 4.7.12): Liver – 14 cms, normal echotexture and outline, PV – 12 mm, spleen –8.3 cms, moderate to gross ascites ++, RK – 8.5 cms, LK – 9.2 cms, grade 1 renal parenchymal disease, B/L pleural effusions.

Ultrasound abdomen (last admission - 4.1.13): Liver – 13 cms, normal, spleen –8 cms, gallbladder-contracted, mild to moderate ascites ++, mild left pleural effusion, RK – 8.4 cms, LK – 9.7 cms, B/L renal parenchymal disease, cystitis.

Compression ultrasound lower limbs: No evidence of deep-vein-thrombosis (DVT) in both lower limbs.

CECT abdomen (1st admission -7.7.12): Small bowel malrotation, stomach normal, duodenum-1st and 2nd parts dilated with collapsed 3rd part, small bowel loops thick walled, proximal jejunum distended with underdistended segment of jejunum in right iliac fossa with adjacent crowding and acute angulations of small bowel loops in pelvis with enteroliths. Gross ascites. Few small subcentimetric lymph nodes in mesentery with no calcification or necrosis.

CECT abdomen (last admission - 8.1.13): Pneumoperitoneum – possible sealed perforation, malrotation, long segment jejunal mural thickening with focal areas of dilatation with few stenotic segments involving proximal/mid jejunal loops, prominent distal jejunal/proximal ileal loops, gross ascites ++ with mid-peritoneal thickening or enhancement, no significant retroperitoneal or mesenteric lymphadenopathy.

Barium meal follow through (BMFT) (11.7.12): Short segment stricture (2 cm) with smooth mucosa involving D3/4 segment with dilatation of proximal duodenum. Another short segment stricture in proximal jejunal loop with mucosal irregularity with grossly distended proximal jejunal loops, rest of jejunum shows thickened mucosal folds. Ileum shows prominent mucosal folds, ileocecal junction and cecum normal.

Endoscopy: Upper gastrointestinal enteroscopy - esophagus-normal; stomach-food residue in fundus, rest normal; duodenum-1st, 2nd parts distended with food residue, narrowing in 3rd part with smooth mucosa, 4th part normal; jejunum- at 15 cm from duodenojejunal flexure nodular ulcerated area with narrowing seen beyond which scope not negotiable. Biopsies were taken from duodenum and jejunum. Colonoscopy- normal up to terminal ileum.

Histopathology: Duodenal biopsy (S-12883/12) - chronic nonspecific inflammation, jejunal biopsy (S-13093/12)-infiltrative disorder like immunoproliferative small intestinal disease or low grade lymphoma with superadded Cytomegalovirus (CMV) infection.

Rest investigations: Bone marrow examination (A-1146/12, 7.8.2012): hypocellular marrow with gelatinous transformation, no evidence of infiltration by lymphoma. Two-dimensional echocardiogram (2D Echo) (3.8.2012) –normal left ventricular systolic (LVS) function, EF – 55-60 %, dilated RA, RV. Urine R/E – albumin +, calcium oxalate crystals + (July, 2012): normal (January 2013); 24 hrs urine protein – 150 mcg/24 hrs, Na+ – 111 mEq/L, Kn -10.2 mEq/L, CK-MB – 136. Lipids- CH-93, TG-85, LDL-16, HDL-13 (January, 2013).

Ascitic fluid analysis

July 2012

January 2013

TLC, DLC

80, P-70 %/L-30 %

5280, P-70 %/L-30 %

Protein

620 mg

1.2 g

Sugar

136

14

SAAG

1.7

 

ADA

3

 

Culture

sterile

E. coli and yeast

Malignant cytology

negative×3

 

Amylase

5

4

Bilirubin

0.1

1.1

TG

11

 

Creatinine

0.2

 

Date

7.7.2012

26.7.2012

8.8.2012

11.9.2012

10.10.2012

5.1.2013

14.1.2013

Hb

10.9

10.0

9.6

11.1

9.3

8.7

8.7

TC

4100

2900

4100

5900

8600

5400

15000,

DC

69/22/7/2

64/30/4/2

64/34/2

66/26/6/2

80/20

62/30/4/2

88/8/3/1

Platelets

3.68 lakhs

4.44 lakhs

4.02 lakhs

5.24 lakhs

4.19 lakhs

4.63 lakhs

0.59 lakhs

ESR

14

40

39

50

   

Date

7.7.2012

8.8.2012

11.9.2012

10.10.2012

5.1.2013

11.1.2013

14.1.2013

Na/K

145/5.5

136/3.7

138/4.9

141/3.9

134/3.8

148/4.5

143/4.0

Urea / Creat

11.7/0.48

20/0.35

13/0.3

18.4/0.3

22/0.4

15/0.5

23/0.6

Ca++ / Phos/Mg++

7.07/3.02/1.7

7.89/4.3/1.67

8.8/1.4/1.86

8.0/2.9/2.2

6.9/4.7/2.2

8.2/4.4/1.5

8.3/4.9/1.9

SGOT/SGPT / ALP

18/21/86

21/21/68

10/17/77

23/18/102

41/34/471

31/27/732

32/33/592

Bili (T)

0.4

0.2

0.3

0.6

0.49

2.9/1.5

4.47/3.42

TP/Alb

4.2/2.6

4.65/2.3

4.5/2.5

5.1/2.7

3.52/1.3

 

4.13/2.5

Amylase

24

      

Lipase

16

      

LDH

272

238

     

Course and Management: This 28 yrs young male presented with history suggestive of subacute intestinal obstruction along with painful small bowel diarrhea and ascites. He was diagnosed to have immunoproliferative small intestinal disease (IPSID) in August 2012 and was started on CHOP regimen along with doxycycline. Subsequently he received 4 more cycles of CHOP regimen. He was readmitted in January 2013 with recurrence of diarrhea with severe malnutrition and anasarca. On 6.1.13 he had pain abdomen and obstipation. CECT abdomen showed progression in length of jejunal stricture and pneumoperitoneum. He was started on broad spectrum antibiotics and supportive therapy. In view of absence of peritoneal signs like guarding, rigidity a possibility of sealed intestinal perforation was considered and surgery consultation was taken who advised conservative management in view of poor general condition. Ascitic fluid analysis revealed secondary bacterial peritonitis and antibiotics were upgraded. He developed hypotension on 14.1.2013, surgery review consultation was taken and a flank drain was placed. Despite supportive treatment he developed a cardiac arrest on 15.1.2013 and could not be revived.

Units Final Diagnosis

Chronic painful small bowel diarrhea with jejunal stricture

Etiology: Primary GI lymphoma (on CHOP regimen)

? Immunoproliferative small intestinal disease

? Non IPSID lymphoma

Intestinal perforation with secondary peritonitis with sepsis

?? CMV enteritis

Severe malnutrition

Intestinal malrotation

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Plenary Session

PLE-1

A comparison between efficacy of 6 months and 9 months of intermittent anti-tuberculous therapy for abdominal tuberculosis (intestinal and peritoneal): A randomized controlled trial

Govind K Makharia, Abhishek Agnihotri, U C Ghoshal, B S Ramakrishna, Sudipto Chaudhary, Manish K Pathak, Asha Mishra, Siddhartha Datta Gupta, Raju Sharma, R M Pandey, Vineet Ahuja, S K Sharma

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110 029, India; Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India; and Department of Gastroenterology, Christian Medical College, Vellore 632 004, India

Background: Whether patients with abdominal tuberculosis (both gastrointestinal and peritoneal) should be treated with six months or nine months is a debatable. There is also a lack of data on the efficacy of short course intermittent therapy in treatment of abdominal tuberculosis. We conducted a multicenter single blinded randomized controlled trial to assess the efficacy of 6 months and 9 months of anti-tuberculous therapy (ATT) in abdominal tuberculosis using directly observed therapy short course (DOTS).

Patients and Methods: Of 499 patients screened, 197 patients with abdominal tuberculosis (gastrointestinal- 154, peritoneal 40, mixed 3) were randomized to receive 6-mo (Group A, n=104) and 9-mo (Group B, n=93) of ATT using DOTS strategy. All patients were evaluated for primary end-point (complete clinical response, partial clinical response, no response, or death) and secondary end-point (mucosal healing). Patients were followed up further for one year after completion of treatment to assess recurrence.

Results: Both groups had similar baseline characteristics, clinical manifestations. Per protocol analysis showed no difference in complete clinical response (91.5 % vs. 90.8 %, p=0.882) between group A and group B. Intention to treat analysis also showed no difference between two groups, complete clinical response being 75 % vs. 75.8 %, p=0.895. Over follow up for one year, one patient had recurrence of disease in group A.

Conclusions: Short course intermittent treatment for 6 months is as effective as 9 months in the management of abdominal tuberculosis. There was no difference in the recurrence rate at one year of follow up. [www.clinicaltrial.gov/ Registration no: NCT01124929].

PLE-2

Development of a modified PIRO (predisposition, injury, response, organ failure) model for predicting kidney failure in patients with acute-on-chronic liver failure - A multinational cohort study of 1,365 patients from AARC database

R Maiwall 1 , S K Sarin 1 , C K Kedarisetty 1 , R Moreau 28,29 , L Anand 1 , A Abbas 5 , D Amarapurkar 6 , A Bhardwaj 2 , A S Bhadoria 2 , C Bihari 3 , A S Butt 7 , C Choudhary 1 , A C Chan 8 , Y K Chawla 10 , A K Dokmeci 11 , H Garg 1 , H Ghazinyan 12 , S Hamid 7 , A **dal 1 , N Kumar 1 , A Kumar 1 , D J Kim 13 , P Komolmit 14 , G K K Lau 15 , G H Lee 16 , L A Lesmana 17 , M Mahtab 18 , Q Ning 19 , V Pamecha 4 , D Payawal 20 , D Rangegowda 1 , A Rastogi 3 , S Rahman 18 , M Rela 21 , A Sahney 1 , V Saraswat 22 , S Shah 23 , G Shiha 24 , B C Sharma 25 , M Sharma 1 , K Sharma 1 , Siam Tan Soek 26 , C Vashisht 1 , Z A Wani 1 , M F Yuen 9 , O Yokosuka 27 of the APASL ACLF Working Party

Departments of Hepatology1, Research2, Pathology3 and Hepatobiliary Surgery4, Institute of Liver and Biliary Sciences, New Delhi, India; Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan5; Department of Gastroenterology and Hepatology, Bombay Hospital and Medical Research, Mumbai, India6; Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan7, Division of Hepatobiliary and Pancreatic Surgery, and Liver Transplantation, Department of Surgery8 and Department of Medicine9, The University of Hong Kong, Hong Kong, China; Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India10; Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey11; Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia12; Center for Liver and Digestive Diseases, Hallym University Chuncheon Sacred Heart Hospital, Gangwon-Do, Republic of Korea13; Division of Gastroenterology and Hepatology, Department of Medicine, Chulalongkorn University, Bangkok, Thailand14; Department of Hepatology, The Institute of Translational Hepatology, Bei**g 302 Hospital, Bei**g, China15; Department of Gastroenterology and Hepatology, National University Health System, Singapore16; Division of Hepatology, University of Indonesia, Jakarta, Indonesia17; Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh18; Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China19; Department of Hepatology, Cardinal Santos Medical Center, Manila, Philippines20; Institute of Liver Diseases and Transplantation, Global Health City, Chennai, India21; Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India22; Department of Gastroenterology and Hepatology, Global Hospitals, Mumbai23; Department of Internal Medicine, Egyptian Liver Research Institute and Hospital, Cairo, Egypt24; Department of Gastroenterology, G B Pant Hospital, New Delhi, India25; Department of Gastroenterology and Hepatology, Selayang Hospital, Malaysia26; Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan27, UMR_S1149, Center for Research in Inflammation (CRI), Inserm and Paris Diderot University28, Paris, DHU Unity, Liver Unit,, Beaujon Hospital, APHP, Clichy, France29

Background and Aim: Kidney dysfunction is an ominous sign in acute-on-chronic liver failure (ACLF) patients. There is however, limited data on predictors of kidney dysfunction in ACLF. The predisposition, injury, response, organ failure  (PIRO) classification was developed to stratify patients with sepsis with different outcomes. We developed a modified PIRO model to identify variables for predicting kidney failure in a multicentric, multinational cohort of ACLF patients (APASL definition).

Patients and Methods: Prospectively collected data from 17 Asian countries using the APASL ACLF Research Consortium (AARC) was analyzed and logistic regression models were developed to assess the best set of covariates for each of the components of PIRO and a combined PIRO model for predicting kidney failure in patients with ACLF. Kidney failure was defined as an increase of serum creatinine ≥2 mg/dL or requirement of renal replacement therapy. Factors considered for univariate analysis for predisposition included patient demographics, severity and etiology of underlying liver disease, baseline biochemical parameters, presence of ascites, comorbidities including chronic kidney disease; for injury-diuretic use, nephrotoxicity, bacterial infections, variceal bleed; for response-components of systemic inflammatory response syndrome and for organ failure-extrarenal organ failures i.e. cerebral, circulatory and respiratory defined according to CLIF-SOFA score.

Results: Of 1,365 patients with ACLF (age 44±12.9 years, 83 % males) with MELD score of 32.6±9.4, 10 % developed kidney failure. Factors significant (p, OR, 95 % CI) on multivariate analysis for P component were high baseline creatinine (≥1) (.<0001, 5.72.39-13.8), high urea (≥35 mg/dL) (0.002, 1.02 1.01-1.03) and high lactate (>2) (0.05, 1.132 (0.99-1.28); for I component, bacterial infections (<0.0001, 2.3, 1.5-3.7), nephrotoxicity (<0.0001, 10.6, 3.7-30.1) and diuretic use (0.012, 2.9, 1.2-6.6); for R component, presence of SIRS (0.02, 1.7 (1.07-2.84)); for O component, circulatory failure (<0.0001, 6.4, 3.78-10.9) and respiratory failure (0.03, 1.7, 1.04-2.97). The combination of these four components into a single-value predictor of kidney failure in the combined PIRO model predicted kidney failure and mortality with an AUROC of 0.90 (p<0.0001, 95 % CI 0.85-0.94) and 0.80 (p<0.0001, 0.76-0.83) respectively. Interestingly the AUROC of the PIRO model for prediction of mortality was better than the MELD, MELDNa and CTP score with AUROC 0.74, 0.70 and 0.67 respectively. Amongst all organ failures, development of kidney failure was an independent predictor of mortality (p=0.007, HR 1.58, 95 % CI 1.13-2.21).

Conclusions: The PIRO model could be a novel approach to identify and stratify ACLF patients at risk of kidney failure as well as mortality. Kidney failure is commonly associated with presence of extra-renal organ failures at baseline and development of kidney failure predicts mortality independent of extrahepatic organ failures.

PLE-3

Combination of granulocyte colony-stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis

Chandan Kumar Kedarisetty , Lovkesh Anand, Ankit Bhardwaj, Ajeet Singh Bhadoria, Paul David, Nirupama Trehanapati, Chhagan Bihari, Archana Rastogi, Hitendra Kumar Garg, Chitranshu Vashishtha, Rakhi Maiwall, Manoj Kumar, Shiv Kumar Sarin

Departments of Hepatology, Research and Pathology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: Patients with decompensated cirrhosis have significantly reduced survival without liver transplantation. Granulocyte colony stimulating factor (G-CSF) has been shown to increase survival in patients with acute-on-chronic liver failure, and erythropoietin promoted hepatic regeneration in animal studies. We performed a double-blind, randomized, placebo-controlled trial to determine whether co-administration of these growth factors improved outcomes of patients with advanced cirrhosis.

Methods: In a prospective study, consecutive patients with decompensated cirrhosis seen at the Institute of Liver and Biliary Sciences, New Delhi (from May 2011 through June 2012) were randomly assigned to groups given subcutaneous G-CSF (5 μg/kg/day) for 5 days and then every 3rd day (12 total doses), along with subcutaneous darbopoietin 40 mcg/week) for 4 weeks (GDP group, n=29), or only matched placebos (control group, n= 26). All patients also received standard medical therapy and were followed for 12 months. Histology was performed on liver biopsies. The primary end-point was survival at 12 months.

Results: Baseline characteristics of patients were comparable; alcohol intake was the most common etiology of cirrhosis. A higher proportion of patients in the GDP group than controls survived until 6 months (82.7 % vs. 57.7 %; p=.03) and 12 months (68.6 % vs. 26.9 %; p=.003). At 12 months, CTP scores were reduced by 48.6 % in the GDP group and 39.1 % in the control group, from baseline (p=.001); MELD scores were reduced by 40.4 % and 33 %, respectively (p=.03). The need for large-volume paracentesis was significantly reduced in GDP group, compared with controls (p<0.05). A lower proportion of patients in the GDP group developed septic shock (6.9 %) compared with controls (38.5 %; p=.005) during follow up. No major adverse events were observed in either group.

Conclusions: In a single-center randomized trial, a significantly larger proportion of patients with decompensated cirrhosis given a combination of G-CSF and darbopoietin survived for 6 and 12 months than patients given only placebo. The combination therapy also reduced liver severity scores and sepsis to a greater extent than placebo. [Clinicaltrials.gov no: NCT01384565].

PLE-4

Heterozygosity of stromelysin-1 promoter polymorphism is associated with gastric cancer

Krishnaveni Devulapalli , Amar Chand Bhayal, P Shravan Kumar, M Uma Devi, M Ramanna, A Venkateshwari

Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad 500 016, India, and Department of Gastroenterology, Gandhi Hospital, Musheerabad, Secunderabad 500 003, India

Background: Gastric cancer (GC), is the third leading cause of cancer death worldwide and the second leading cause of cancer death in India. It is a multifactorial disorder mediated by genetic, epigenetic and environmental factors. GC has been reported to be much frequent in South Indian population compared to that of North India. A single nucleotide 5A/6A polymorphism (rs3025058) at -1171 of the stromelysin-1 (MMP-3) promoter is resulting due to ins/del of adenine thought to have impact on the transcriptional activity and thus increasing the risk for tumor formation.

Aim: To understand the role of stromelysin-1 promoter 5A/6A polymorphism in the etiology of GC in south Indian population.

Methods: The present case-control study considered 208 GC patients and 226 controls. Genomic DNA was isolated from blood samples of patients and controls. The genoty** of 5A/6A polymorphism was carried out by ARMS-PCR method followed by agarose gel electrophoresis.

Results: The frequency of 5A/5A, 5A/6A and 6A/6A genotypes in patients were 7.69 %, 76.92 % and 15.38 %, while in controls they were 5.31 %, 86.73 % and 7.96 %, respectively. There was a significant difference in the distribution of 5A/6A genotype in patients compared to the controls (p<0.05) exhibiting 50 % increased risk and we found a significant association of 5A/6A genotype (p<0.05) with epidemiological factors such as age, sex, diet, alcohol, smoking, consanguinity and familial incidence indicating association of heterozygosity with increased risk for GC.

Conclusion: The present study showed an association of stromelysin-1 promoter polymorphism with GC, and thus thought to be involved in the etiology of GC.

PLE-5

Acute-on-chronic liver failure due to acute hepatic insult: An Eastern perspective

Shalimar, Dharmendra Kumar, Padmaprakash Kadavoor Vadiraj, Baibaswata Nayak, Shyam Prakash, Bhaskar Thakur, Prasenjit Das, Subrat Kumar Acharya

Departments of Gastroenterology, Pathology and Biostatistics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India

Background: In acute-on-chronic liver failure (ACLF), the effect of distinct etiologies, underlying silent or overt chronic liver disease and other predictors of prognosis is not clear.

Patients and Methods: In a prospective study, 213 consecutive ACLF patients were evaluated until death or discharge. Etiology of acute hepatic insult, underlying silent or overt chronic liver disease (CLD), organ failure (OF), other complications and disease outcomes were evaluated, and prognostic scores including model for end-stage liver disease (MELD), acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) were calculated.

Results: The most common causes of acute hepatic insult were alcohol, hepatitis B virus (HBV) and hepatitis E virus (HEV) in 77 (33.3 %), 42 (19.7 %) and 39 (18.3 %) cases respectively. The etiology of CLD was alcohol, HBV and cryptogenic in 85 (40 %), 52 (24 %) and 50 (23 %) cases. The mortality in HEV-ACLF was significantly lower (12.8 % vs. 33 % to 54 % in other etiologies; p<0.001). With similar SOFA, APACHE II and MELD scores, the mortality was 33.9 % in the silent CLD group (112, 52.6 % cases) as compared with 53.5 % in the overt CLD group (101, 47.4 %; p=0.005). Independent predictors of mortality included hepatic encephalopathy (early, OR:6.01; advanced OR:18.36), renal failure (creatinine >1.5 mg/dL, OR:9.68), elevated serum arterial ammonia (>92¼  mol/L, OR:4.30) and etiology of acute hepatic insult (HBV, OR:10.266; alcohol, OR:35.52 and cryptogenic, OR:10.39). With increasing number of organ failures, the mortality increased linearly (p=0.001).

Conclusion: The etiology of acute hepatic insult, silent underlying CLD and occurrence of OF are important predictors of outcome in ACLF. Important causes include alcohol and hepatitis viruses.

PLE-6

Early acinar injury and immune response in acute pancreatitis in humans

Aparna Jakkampudi * , Ramaiah Jangala * , C Ramji * , Sasikala Mitnala * , G V Rao # , D N Reddy # , Rupjyoti Talukdar* #

*Asian Healthcare Foundation, Hyderabad, India, and #Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500 082, India

Background and Aim: The early intra-acinar events and immune response in human acute pancreatitis is not clear. Although experimental pancreatitis models in rodents have elucidated these mechanisms, these may not be similar in humans. In the present study we aimed to investigate the early intra-acinar events in clinical AP, and the inflammatory response in an experimental setting using human pancreatic tissues.

Methods: Normal human pancreatic tissue slices were prepared and exposed to FAEE and TLCS for different time intervals. Subcellular fractionation was performed on tissue homogenates, and trypsin and cathepsin B activities were estimated in the fractions. Type of cell injury was evaluated by histology, immunohistochemistry and western blot. Cytokine release by exposed acinar cells and activated PBMCs as well as from acute pancreatitis patients serum samples were evaluated by FACS. Normal pancreata were exposed to conditioned medium from activated PBMCs to study role of cytokines in inducing acinar injury.

Results: Trypsin and cathepsin B activities at different time intervals revealed significant redistribution of trypsinogen and cathepsin B at 30 minutes. H&E showed significant tissue injury in the TLCS and FAEE treated tissues. IHC results indicated the presence of LC3 (marker of autophagy). Release of cytokines in media of treated acinar tissue and activated PBMCs was significantly higher compared to controls. Exposure to cytokine containing media induced healthy acinar tissue to secrete cytokines.

Conclusion: Our data suggest that there is zymogen:lysosome colocalization/autophagy, which results in acinar cell injury and release of cytokines which can activate PBMCs that can lead to further acinar injury.

Young Investigator Award Session

YIA-1

Dendritic cell subsets and expression of DC-SIGN in progression of hepatitis B infection from acute to chronic disease: A novel insight through toll-like receptors and related intracellular signalling molecules

Sukriti Sukriti , Nirupma Trehan Pati, Manoj Kumar, Syed S Hissar, Shiv Kumar Sarin

Institute of Liver and Biliary Diseases, D-1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: Dendritic cells (DC’s) are known immune sentinels. DC–specific intercellular adhesion molecule 3–grabbing nonintegrin (DCSIGN) and toll-like receptors (TLRs) which are pathogen recognition receptors are present on DC’s to promote pathogen recognition, uptake and presentation of antigen and potentiates the interaction with T cells which represents the major “link” between innate and adaptive immunity. We hypothesize; insufficient generation of immune surveillance in chronic hepatitis B might be because of impairment of frequencies and functional ability of DC’s, expression of DC-SIGN and TLR’s. We aimed to monitor temporal changes in DC’s and DCSIGN, TLR’s during acute phase in comparison to chronic hepatitis B infection. Also using HBV vaccine as a model to investigate the initial changes in TLR’s and its adaptor molecules.

Patients and Methods: Twenty-eight subjects were included; acute viral hepatitis B (AVH-B, n=8) were serially followed up; chronic hepatitis B (CHB, n=10) and healthy controls (HC, n=10). Also, four healthy volunteers received hepatitis B vaccine (attenuated HBsAg) and followed up at day 0, 3, 7, 15. AVH-B patients. PBMCs were isolated and stained before and after stimulating with polyI:C, CpGODN and LPS with flourochrome labelled antibodies. Evaluated frequency of myeloid DC’s (mDC) (CD11c+, BDCA1+), plasmacytoid DC’s (pDC’s) (CD123+, BDCA1+), intracellular IFN-γ production and expression of DCSIGN, TLR2,3,4 on mDC’s and TLR9 on pDC’s. mRNA levels of major adaptor molecules of TLR pathway; Myd88, TRAF6 and cytokines IL-2, IL-6 , TNF-α , IFN-α was measured by RT-PCR.

Results: Frequencies of both subsets of DC’s i.e. mDC’s and pDC’s, was found significantly higher in acute and naïve chronic HBV patients than healthy control (p<0.00, p<0.01) but no difference among AVH-B vs. CHB. Functionally impaired DC’s were seen with significant low IFN-γ production and low DCSIGN expression (p<0.04, 0.00) in CHB patients. Even after stimulations by TLR agonist, no changes were found. The adaptor molecule of TLR’s, the MyD88 mRNA levels were also down regulated along with the cytokines IL-6, IFN-α. On follow up of AVH-B patients, found temporal changes in DC’s while mDC’s frequency was significantly highest at wk 4, whereas pDC’s at wk 6 than wk 0 (p<0.02, 0.01) along with the DCSIGN on mDC’s expression increased linearly from wk 0 to wk 4 during acute phase (wk 0 28 % to wk 4 72 %, p<0.00). On follow up after HBV vaccine, found TLR 2, 3, 4, 9 expression was highest at day 3 after vaccination.

Conclusions: (i) Subsets of dendritic cells are phenotypically intact but functionally impaired in CHB compared to seroconverted AVH-B patients, (ii) During acute phase pDC’s comes late in generation of effective immune response, (iii) DC SIGN expression is temporally increased in acute phase HBV infection, while is significantly low in CHB, indicating its key role in persistent infection, (iv) Toll like receptors gets activated very early at day 3 of the pathogen encounter. These novel observations would pave way for prognostication and development of antiviral strategies for chronic HBV infection.

YIA-2

Role of CK 18 (M30) in predicting mortality in patients with acute liver failure

Chetnya Malik , Rajib K Hazam, Premashis Kar

Department of Medicine, Maulana Azad Medical College and Associated Lok Nayak Hospital, Bahadur Shah Zafar Marg, New Delhi 110 002, India

Introduction: Poor prognosis of acute liver failure (ALF) is well known. Although numerous prognostic criteria have been established, they lag in their predictive accuracy when applied to Asian population. Also with the recent interest in cell death markers, we undertook this study to assess the role of cytokeratin 18 (M30) in ascertaining the prognosis of patients with ALF and thus identify who all will benefit from a liver transplant.

Methods: Forty-five adult patients with ALF were evaluated and managed in ICU in the Department of Medicine, of Lok Nayak Hospital, New Delhi, India. Routine blood investigations and CK 18 (M30) levels were done.

Results: The mean cleaved CK18 [M30] levels in ALF patients who expired were significantly higher than those who survived. We also found that there was statistically significant difference in total leukocyte count, serum creatinine, INR and cleaved CK18 M30 levels among those that survived vs. expired. Multivariate analysis found that all these independently predict mortality. The predicted probability of mortality can be found from the equation: Computed Score=-0.404+(0.074*INR)+(0.00004513*TLC)+ (0.0001*M30).

Conclusion: The results of our study suggest that initial serum CK 18 (M30) levels predict outcome in ALF patients. We suggest that ALF patients with serum cleaved CK18 [M30] levels at admission more than 988.07 mLU/mL are candidates for liver transplantation, which can be life saving for these patients.

YIA-3

Metformin reduces hepatic resistance and portal pressure in cirrhotic rats

Dinesh M Tripathi 1,2 , Eva Erice 1 , Hector Garcia-Caldero 1 , Shiv K Sarin 2 , Jaime Bosch 1 , Jordi Gracia-Sancho 1 , Juan Carlos Garcia-Pagn 1

1Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS, Hospital Clinic Barcelona, Liver Unit, CIBEREHD, Barcelona, Spain, and 2Institute for Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: Increased hepatic vascular resistance is the primary factor in the development of portal hypertension (PH). In other vascular beds, metformin ameliorates vascular cells function. Our study was aimed to evaluate the effects of metformin on hepatic and systemic hemodynamics in cirrhotic rats. In addition, we studied the possible interaction between metformin and propranolol (Prop), the current standard treatment of PH.

Methods: CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 week, before measuring hemodynamic parameters (MAP, portal pressure-PP, portal blood flow-PBF, hepatic vascular resistance-HVR), and molecular/cellular potential mechanisms. In a sub-group of rats, the hemodynamic response to acute prop (5 mg/kg IV) was assessed. Effects of metformin±prop on PP and MAP were validated in CBDL-cirrhotic rats.

Results: Metformin-treated CCl4-cirrhotic rats had lower PP and HVR than vehicle-treated rats, without significant changes in MAP or PBF. Prop further reduced PP. Metformin caused a significant reduction in liver fibrosis (Sirius red), HSC-activation (alpha-SMA and RhoK), hepatic superoxide (dihydroethidium staining) and oxidative stress-mediated NO-scavenging (protein nitrotyrosination). No significant changes in AMPK or eNOS were observed. CBDL-cirrhotic metformin-treated rats also had significantly lower PP than those treated with vehicle without significant changes in MAP. Prop administration reduced PP.

Conclusions: Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of propranolol. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation.

YIA-4

Alteration of hepatitis B virus genomic population in inactive carriers

Panyala Balkumar Reddy 1, Rathindra Mohan Mukherjee 1, Mitnala Sasikala 1, Gelli Veena Shravanthi 1, Padaki Nagaraja Rao 2, Mithun Sharma 2, Duvvuru Nageshwar Reddy 2

1Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad, India, and 2Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500 082, India

Introduction: Hepatitis B virus (HBV) can exist as closely related yet genetically distinct variants known as quasispecies where variants possessing highest environmental fitness may exist as predominant. In our previous study we evaluated an in-house PCR assay for identification of possibly coexistent majority/minority genomic fragments as diagnosis escape variant (DEV) population which remain undetectable by a commercially available real time PCR assay. The present study focused on detection of DEVs in different disease categories in HBV infection in order to evaluate their prevalence in each group.

Methods: One hundred and eighty-six treatment naive, HBsAg positive and anti-HCV negative subjects were enrolled for the study and categorized into acute hepatitis B (AHB), immune tolerant (IT), HBeAg-positive chronic (EPCHB), inactive carriers (IC), and HBeAg-negative chronic (ENCHB) groups. HBV DNA was extracted from patient's sera and quantification was done by real-time PCR. In-house PCR assay was run to detect the wild and diagnosis escape variant population and band intensities were semi quantified.

Results: Out of 186 HBV DNA positive subjects, 78 % were male, and mean age was 39 years. Mean ALT and HBV DNA levels were 131 U/L and 5.43 log copies/mL respectively. A total of 68 patients were detected positive for DEV population.

Conclusion: In conclusion, employing a novel strategy for detection of both wild type and DEV in a single subject, the present study showed for the first time that about 36 % of HBV infected subjects harbor DEV population. Furthermore, nearly 64 % of inactive carriers harbor DEV as majority genomic population replacing the wild type HBV.

YIA-5

Can early endoscopic ultrasound predict pancreatic necrosis in acute pancreatitis?

Surinder S Rana , Deepak K Bhasin, Vishal Sharma, Ravi Sharma, Vinita Chaudhary, Puneet Chhabra

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Presence of pancreatic/extrapancreatic necrosis (PN/EPN) is an important prognostic indicator in acute pancreatitis (AP) and its early detection is a challenge. Endoscopic ultrasound (EUS) provides high resolution images of pancreas but there is paucity of data on its role in AP.

Methods: Consecutive patients with AP seen at our center from December 2012-November 2013 and presenting within 5 days of onset of symptoms were prospectively enrolled. EUS was done on the day of admission with a radial echoendoscope and pancreatic/peripancreatic findings were compared with the abdominal CT findings done on day 7.

Results: Of 46 patients evaluated, 14 were excluded and 32 patients (22 M; age 40.68±12.46 years) underwent EUS at admission. The etiology of AP: alcohol in 16, gallstones in 13 and idiopathic in 3 patients. Necrotizing pancreatitis was present in 20 (62 %) patients and mean CTSI was 6.45±2.96. In patients without PN (n=12), EUS revealed normal echo pattern in 6 patients and diffusely hyperechoic and enlarged pancreas in 6 patients. In patients with PN/EPN, EUS revealed multiple hypoechoic areas (>5 mm) in 5 patients, multiple hyperechoic areas (>5 mm) in 7 patients and mixed hypo and hyperechoic areas in 8 patients. Also 13 of these patients had peripancreatic hypoechoic areas that correlated with EPN. Moreover, EUS detected CBD stones in two patients, pleural effusion in 17 patients and ascites in 15 patients.

Conclusion: EUS done at admission can detect pancreatic necrosis reliably and also detect coexistent disorders like common bile duct stones.

YIA-6

A randomized, comparative open label study of imipenem versus cefepime in difficult to treat spontaneous bacterial peritonitis

Ankur **dal , R Maiwal, C Vashishta, M Kumar, K N Kumar Chandan, V Bhatia, Y K Joshi, S K Sarin

Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India

Background: Spontaneous bacterial peritonitis (SBP), in the presence of bacterial resistance and/or failure of first-line antibiotic therapy; third generation cephalosporins (3rd GC), has poor outcome. Carbapenems are often used empirically in this scenario. cefepime, a fourth generation cephalosporin, may provide equal efficacy at a low cost and may also prevent emerging carbapenemase resistant strains.

Patients and Methods: In a prospective study, consecutive cirrhotics with difficult to treat SBP (DTT-SBP) owing to hospital acquired SBP (beyond 48 h of admission), microbial resistance or nonresponse (no resolution of SBP at 48 h) or recurrence of SBP on 3rd GC were randomly assigned to either cefepime group (1 g thrice daily intravenously) (n=88) or imipenem group (1 g thrice daily intravenously) (n=87) along with standard medical therapy. Diagnostic paracentesis was done at baseline and repeated at 48 h and 5 days after randomization. Primary end-point was to determine early response (reduction in ascitic fluid absolute neutrophil count (ANC) by >25 % at 48 h and/or negative ascitic fluid culture) and treatment failure (>250 cu/mm ANC at day 5). Patients were followed up for a period of 3 months.

Results: Of the 957 diagnostic paracentesis among 1,200 admitted decompensated cirrhotics, 253 (26.4 %) had SBP; 175 (69.6 %) of them were diagnosed with DTT-SBP. The baseline characteristics were comparable in the two groups. The DTT-SBP was mainly due to resistance to 3rd GC (cefepime group -38.3 % and imipenem group -48.7 %; p-0.06). Early response (58.6 % vs. 51.7 %; p-0.36) and treatment failure rates (37.9 % vs. 39.1 %; p-0.87) were comparable in the two groups with no difference in mortality at 2 week, 1 and 3 months. Treatment failure was independently associated with early non-response [OR-10.77 (95 % CI-4.01-28.95)] and development of septic shock [OR-3.43 (95 % CI-1.18-9.99)]; the latter being the main pre-terminal event in both groups (32.3 % vs. 35.6 % respectively). On multivariate analysis, presence of AKI at enrolment [HR-2.55 (95 % CI: 1.27-5.08)], pneumonia [HR-2.92 (95 % CI: 1.48-5.76)], septic shock [HR-2.15 (95 % CI: 1.09-4.23] and treatment failure for SBP [HR-4.63 (95 % CI: 2.02-10.58)] predicted poor outcome.

Conclusions: In hospitalized cirrhotic patients with SBP and known risk factors for treatment failure, cefepime showed comparable efficacy and survival to imipenem. Early nonresponse to therapy at 48 h and onset of septic shock were the strongest predictor of treatment failure and mortality and should indicate more aggressive therapy. [Clinicaltrials.gov no: NCT01852630].

Presidential Poster

Plenary

PPLE-1

Characterization of biofilms occluding stents retrieved from patients with biliary and pancreatic diseases

Chetana Vaishnavi, Prashant Kapoor, Rakesh Kochhar

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Biofilms comprise of matrix-enclosed bacterial population which gets attached to surfaces such as that of stents. We quantified the biofilm mass as well as characterized the matrix and the diverse bacterial community in biofilms of stents retrieved from patients with biliary and pancreatic diseases.

Materials and Methods: Stents (n=105) obtained during ERCP from patients with biliary and pancreatic diseases formed the basis of investigation. Quantification of biofilm mass, protein and polysaccharide in the biofilms were done. The known and unknown bacteria in the biofilms were respectively identified by PCR using 16S rRNA sequences and by sequencing selected bands excised from gel from the amplified PCR products.

Results: The patients comprised of 56 males and 49 females with age range 16-86 years. The clinical presentation of patients included presence of common biliary duct (CBD) stones (n=63) pancreatitis (n=34) and CBD stricture (n=23). The biofilm mass ranged from 0 to 1.1001 OD, proteins from 0 to 1.21 mg/mL and polysaccharide from 0.012 to 0.107 mg/mL. The most common bacteria identified in the biofilms were pseudomonas (n=34), serratia (n=29), Klebsiella (n=24), citrobacter (n=23), streptococcus (n=17), Escherichia coli (n=17), Aeromonas (n=17), proteus (n=14), Enterococcus (n=13), Enterobacter (n=12) and staphylococcus (n=25). Among the uncommon bacteria found responsible for occluding a large number of stents the commonest were Stenotrophomonas maltophila (n=13), Enterococcus faecalis (n=6), pseudomonas aeruginosa (n=5) and Bacillus cereus (n= 5).

Conclusion: Biofilms in the stents of patients with biliary and pancreatic diseases were enclosed in a protein/polysaccharide matrix with numerous organisms of enteric origin.

PPLE-2

Relation between transition zone and distal breaks in dysphagia and gastroesophageal reflux disease

M Srinivas , V Jayanthi

Department of Gastroenterology, Global Health City, Chennai 600 100, India

Introduction: Peristaltic breaks in high resolution esophageal manometry (HREM) occur in both proximal and distal segments. These may exaggerate the transition zone (TZ) contributing to gastroesophageal reflux disease (GERD) and dysphagia.

Aim: Study the relationship between segment breaks in GERD and dysphagia by test posture.

Methods: Excluding achalasia and post-fundoplication, 112 adult HREM (minimum 5 x 5 mL water swallows, 16-channel water perfused catheter) evaluations for dysphagia and GERD in supine/upright postures were analyzed retrospectively. The TZ and distal break (DB) lengths were classified as no (<2 cm), small (2-5) and large (>5). The TZ break was correlated with DB by indication and posture using Mann-Whitney U test to compare absence and presence of DB in various TZ categories between postures.

Results: In GERD, ~50 % had TZ breaks irrespective of posture with DB in 36 % of them. Even in absence of TZ breaks, 7/42 (16.6 %) had DB, especially in upright posture (p<0.01). In dysphagia, unlike GERD, upright posture was associated with more TZ breaks than supine (48 % vs. 23 %) and DB occurred only in presence of small TZ breaks (4/9 vs. 0/2 supine, p=0.05). DB did not occur in absence of TZ breaks in either posture.

Summary: TZ breaks occurred in both GERD and dysphagia. More breaks occurred in the latter in upright posture. Both TZ breaks and DB were common in upright position for both indications, suggesting that upright HREM may be better for assessing dysphagia and GERD.

Table Correlation with distal breaks, basal LESp and IRP in dysphagia and GERD

Indication (supine/upright)

TZ break (N)

Basal LESp (mmHg)

(median, range)

IRP (mmHg)

(median, range)

Distal break ( N )

<2 cm/2-5 cm/>5 cm

Size (cm)

Supine

Upright

Supine

Upright

Supine

Upright

Supine

Upright

Dysphagia

(13/21)

Supine: 8 men, median age 51

Up: 11 men, median age 53

< 2

10

(77 %)

11

(52 %)

20.5

(0 - 62.5)

15

(1 - 67)

16.3

(7.8 - 32.4)

13.9

(4.2 - 61.6)

10 / 0 / 0

10 / 1 / 0

2 – 5

2

(15 %)

9

(43 %)

42

12

(1 - 48)

23.8

6.9

(3.8 - 26.9)

2 / 0 / 0

4 / 1 / 4

> 5

1

(8 %)

1

(5 %)

19

16

8.3

13

0 / 0 / 1

0 / 1 / 0

GERD

(35/43)

Supine: 25 men,

median age 39

Up: 32 men, median age 39

< 2

20

(57 %)

22

(51 %)

13

(0 - 40.5)

10

(0 - 54)

8.8

(1.5 - 19.2)

9.9

(3.6 - 21.4)

19 / 1 / 0

16 / 5 / 1

2 – 5

10

(29 %)

12

(28 %)

9.5

(1 - 30)

10.5

(2 - 24)

6.3

(3.4 - 36.7)

8.7

(5.6 - 14.2)

7 / 3 / 0

8 / 1 / 3

> 5

5

(14 %)

9

(21 %)

6

(1 - 23)

5

(4 - 17)

3.8

(3.1 - 14.4)

5.2

(2.4 - 11.7)

2 / 0 / 3

3 / 0 / 6

PPLE-3

Impact of genetic predisposition on natural history of idiopathic acute and recurrent acute pancreatitis in children

Ujjal Poddar , Surender Kumar Yachha, Amrita Mathias, * Gourdas Choudhuri

Departments of Pediatric Gastroenterology and *Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014, India

Background: Genetic predisposition in childhood idiopathic acute (AP), recurrent acute pancreatitis (RAP) and its consequences are unknown. We studied frequency of genetic markers (SPINK1, PRSS1 and CFTR) in idiopathic AP, RAP, chronic pancreatitis (CP) and tested the hypothesis genetically predisposed AP, RAP cases are destined to develop CP.

Methods: Genetic mutations were studied in 208 subjects [68 children with idiopathic pancreatitis (AP 24, RAP 22, CP 22), 115 parents and 25 age/sex matched controls]. Common mutations for SPINK1 (N34S), PRSS1 (R122H) and CFTR (delta F508 and 5T) were analyzed by PCR-RFLP.

Results: Mean age of cases was 13.4±2.5 years. Overall, 30 cases (SPINK1: 26 and 4 CFTR 5T) and one control (SPINK1) had mutations (p=0.0001). Odds ratio of having genetic mutations in AP was 10.67 (95 % CI: 1.22 to 93.13), RAP 20 (95 % CI: 2.28 to 175.05) and CP 28.80 (95 % CI: 3.29 to 252.07). The prevalence of SPINK1 mutation was similar in CP and RAP (45.5 % each). Interestingly, 6 (25 %) children with AP had SPINK1 mutations (p<0.05), all had severe pancreatitis and four had homozygous mutations. On follow up, 5 children with and one without mutations in AP group developed CP (p=0.004) and 38 % of RAP progressed to CP more often with mutations (6/9 vs. 2/12, p=0.03).

Conclusions: Almost 50 % of idiopathic CP, RAP and 25 % of AP in children are genetically predisposed. Presence of genetic mutations in AP and RAP increases the risk of develo** CP. Mutation-analysis may help in identifying subset of AP who will progress to CP.

PPLE-4

Risk of celiac disease in the first and second degree relatives of patients with celiac disease: A meta-analysis

Prashant Singh , Shubhangi Arora, Suman Lal, Tor A Strand, Govind K Makharia

Department of Medicine, Massachusetts General Hospital, Boston, USA; Department of Medicine, Brigham and Women’s Hospital, Boston; USA, Max Healthcare, Gurgaon, India; Medical Services Division, Innlandet Hospital Trust, Lillehammer, Norway; Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India

Introduction: First-degree relatives (FDRs) of patients with celiac disease (CeD) are at high risk for CeD and prevalence among them varies widely from 1.6 % to 44 %. There is a lack of data on exact prevalence of CeD among various specific relations such as sister, brother, mother, father, son and daughter. We conducted a meta-analysis to find out above mentioned answers.

Methods: On search of literature using MeSH keywords "celiac disease" "first-degree relatives" and "family", 697 articles appeared of which 49 articles were included. Diagnosis of CeD was based on standard criteria. Pooled prevalence with 95 % confidence intervals (CI) were calculated for FDRs, second degree relatives (SDRs), and specific relations.

Results: Pooled prevalence of CeD in 10,183 FDRs was 7.2 % (95 % CI 6.7 % to 7.8 %) and 2.3 % (95 % CI 1.3 % to 3.8 %) in 642 SDRs. Pooled prevalence of CeD was highest in siblings (9.4 %) and lowest in parents (3.8 %). Female FDRs had higher prevalence than male FDRs (9.6 % vs. 7.3 %). Sisters (18.6 %) and daughters (18.3 %) had significantly higher prevalence of CeD than other FDRs. There were also differences in pooled prevalence of CeD in FDRs according to their geographic location, highest being in USA.

Conclusions: Pooled prevalence of CeD among FDRs is 7.2 % and varies considerably with the relationship to the index patient. While, sisters and daughters are at highest risk (1 in 6), risk in sons is 1 in 10, brothers is 1 in 8 and parents is 1 in 22. The risk of CeD in FDRs also varies according to geographical location.

PPLE-5

Systemic inflammatory response syndrome at admission is a predictor of acute kidney injury development and mortality in hospitalized patients with severe alcoholic hepatitis

Rakhi Maiwall 1 , Suman Kumar 2 , Zeeshan Wani 1 , Manoj Kumar Sharma 1 , C Vashishtha 1 , Shiv Kumar Sarin 1

1Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India, and 2Department of Hematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India

Background: Systemic inflammatory response syndrome (SIRS) is associated with an increased risk of hepatic encephalopathy (HE), renal failure and poor outcome in patients with acute liver failure, however this is not reported for severe alcoholic hepatitis (SAH).

Aim: To look at SIRS at baseline as a predictor of development of acute kidney injury (AKI) and its progression including mortality in patients with SAH.

Methods: Consecutive in-patients with SAH (discriminant function ≥32) without AKI at baseline were included and followed for the development and progression of AKI (defined by AKIN criteria).

Results: Of the 427 patients (mean age 45.5±9.5, 416 males), SIRS at baseline was present in 312 (73 %). AKI developed in 143 (33.5 %) of which 62 (14.5 %) had progression of AKI. Presence of SIRS significantly correlated with serum creatinine (p=0.001), serum sodium (p=0.01), serum bilirubin (p=0.003) and DF score (p=0.001). SIRS, presence of hepatic encephalopathy, and serum creatinine at baseline were significant predictors on univariate analysis for AKI development. On multivariate analysis, SIRS predicted both AKI development (p<0.001, OR 2.7, 95 % CI 1.5-4.6) and AKI progression (p=0.05, HR 2.1, 95 % CI 1.1-4.6). Resolution of AKI also had a significant inverse association with SIRS (p=0.05). High MELD score (≥18) (p=0.008, HR 2.1, 95 % CI 1.2-3.6), in-hospital progression of AKI (p=0.01, HR 1.8, 95 % CI 1.1-2.9) and SIRS (p=0.001, HR 2.9, 95 % CI 1.5-5.7) were significant predictors of short-term mortality at 1 and 3 months.

Conclusion: SIRS at admission predicts both development and in-hospital progression of AKI as well as short-term mortality in patients with SAH. This could definitely have a therapeutic and prognostic implication.

PPLE-6

Acute kidney injury in patients with acute-on-chronic liver failure, is different from patients with cirrhosis

Rakhi Maiwall 1 , Suman Kumar 2 , Chhagan Bihari 4 , Suman Lata Nayak 3 , Archana Rastogi 4 , Chandan Kumar 1 , Chitranshu Vashishtha 1 , Manoj Kumar Sharma 1 , Vikram Bhatia 1 , S K Sarin 1

1Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India; 2Department of Clinical Hematology, Command Hospital [Eastern Command], Kolkata; 3Departments of Nephrology; and 4Pathology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: Acute kidney injury (AKI) is reported at prevalence of 20 % in cirrhotics and is associated with an ominous prognosis. There are no large studies looking at AKI based on acute kidney injury network (AKIN) criteria and no comparative studies comparing AKI in acute-on-chronic liver failure (ACLF) to decompensated cirrhotiics. We investigated the prevalence, spectrum, natural history and outcome of AKI in patients with ACLF (n=534) and compared it with a cohort of hospitalized patients with cirrhosis (n=2083).

Methods: Serial creatinine up to day 30 or until death or recovery was recorded and all patients were assessed for the presence and development of AKI (AKIN criteria).

Results: KI was more common in ACLF (50.5 % vs. 32.3 %; p<0.0001) and was associated with increased mortality (59.9 % vs. 41.3 %; p<0.0001). Presence of ACLF compared with cirrhosis was associated with a six-fold increased risk of AKI (p<0.0001, OR 6.4 95 % CI 4.9-8.3) on multivariate analysis. There was also a significant difference in the spectrum of AKI (p<0.0001) with pre-renal volume responsive AKI as the most common cause of AKI in cirrhosis while hepatorenal syndrome (HRS) in patients with ACLF. HRS in patients with ACLF had a significantly inferior response to vasoconstrictors (p<0.05) with an accelerated progression to AKIN stage 3 (p<0.0001), more commonly associated with bacterial infections (24 % vs. 18 %) and associated with higher mortality (p<0.0001). Of all patients with AKI, no difference was seen in the AKIN stage at baseline however, a significant difference was noted in the peak AKIN stage (p<0.0001) with progression to AKIN stage 3 requiring RRT (23.5 % vs. 12.6 %) significantly more common in ACLF (p<0.0001). Progression of AKI and presence of AKI in ACLF compared with cirrhosis patients, was associated with a significantly higher mortality on multivariate analysis.

Conclusions: AKI in ACLF is more common, with a different spectrum, natural course and mortality as compared to patients with cirrhosis. ACLF patients have an “accelerated HRS” which responds poorly to vasoconstrictors and is associated with a higher mortality signifying a different pathogenetic basis. Prevention and early detection of AKI should hence be considered in ACLF patients.

PPLE-7

Efficacy of carvedilol in early primary prophylaxis of esophageal varices in cirrhosis- A double blind randomized placebo-controlled trial

Ankit Bhardwaj 2 , Chandan Kumar Kedarisetty 1 , Chitranshu Vashishtha 1 , Ajeet Singh Bhadoria 2 , Ashok Choudhary 1 , Ankur **dal 1 , Naveen Kumar 1 , S M Shasthry 1 , Rakhi Maiwall 1 , Manoj Kumar 1 , Shiv Kumar Sarin 1

Hepatic Hemodynamic Lab., Departments of Hepatology1 and Clinical Research2, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: The median rate of progression of small to large varices is 5 % to 23 % per year. Carvedilol has been shown to be effective in primary prophylaxis for large varices. We investigated the utility of carvedilol in small varices.

Patients and Methods: In a prospective double blind study, consecutive cirrhotic patients with small varices were randomly assigned to receive either carvedilol (n=70) or placebo (n=70). Endoscopic assessment for variceal size was done at baseline and every six months for 24 months. Hepatic vein pressure gradient (HVPG) was measured at baseline and at one year. The primary end-point was progression to large varices.

Results: Baseline characteristics were comparable in carvedilol and placebo groups, including CTP (8.40±1.96 in carvedilol group and 8.49±1.66 in placebo group, p=0.78), MELD (9.21±2.60 and 9.67±2.75, p=0.31) scores and baseline HVPG (14.49±4.31 and 14.84±4.69 mmHg, p=0.64) respectively. The mean carvedilol dose administered was 12±1.67 mg/day and the target heart rate achieved was 58±3 beats/min. In the intention-to-treat analysis, a lower proportion of patients in the carvedilol group than controls progressed to large varices until 24 months (22.8 % vs. 41.9 %) with mean time to development of large varices was 20.5 months (95 % CI 18.8-22.1) in carvedilol group and 17.9 months (95 % CI 15.9-19.8) in placebo group, p=0.04. The cumulative probability of survival at 24 months in carvedilol and placebo group was 98.4 % and 90.9 % respectively (p=0.05). At 12 months, HVPG was reduced by 7.47 % in the carvedilol group and 6.54 % in the placebo group, from baseline (p=0.89). No patient had variceal bleed in either group. No major adverse events were observed in either group.

Conclusions: In a single-center randomized controlled trial, carvedilol was found effective in delaying the progression of small to large varices compared to placebo at two years with significant survival benefit. [Clinicaltrials.gov no: NCT01196507].

PPLE-8

Effect of duration of cholecystectomy on orocecal transit time and small intestinal bacterial overgrowth in gallstone patients

Satya Vati Rana , Jaspreet Kaur, Surendra Sharma, Aastha Malik, Rajesh Gupta, Vikas Gupta, Saroj Kant Sinha

Department of Super Specialty of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Aim: Effect of duration of cholecystectomy on orocecal transit time and small intestinal bacterial overgrowth in gallstone patients.

Materials and Methods: One hundred and twenty-eight gallstone patients of either sex, aged between 18-68 years, diagnosed by ultrasound were enrolled. Seventy-nine out of 128 patients were pre-cholecystectomy and then followed after 4-6 months of cholecystectomy. Forty-nine patients were those who had gallbladder removal 2-15 years before study and reported gastrointestinal symptoms, as late post-cholecystectomy. Orocecal transit time (OCTT) and small intestinal bacterial overgrowth (SIBO) were measured by noninvasive lactulose and glucose breath tests respectively.

Results: Out of 128 gallstone patients, 89 (69.5 %) were females. Mean±SD of age in female patients was 45.0±11.7 years and that of males 49.0±12.4 years. OCTT increased significantly (p<0.01) from 125.9±28.6 to 145.8±30.5 minutes after 4-6 months of cholecystectomy. Among late post-cholecystectomy patients, OCTT was observed to be 159.2±37.8 minutes, which was significantly higher when compared with OCTT in pre-cholecystectomy patients. SIBO was present in 10/79 (12.7 %) gallstone patients before cholecystectomy and 11/79 (13.9 %) in gallstone patients post-cholecystectomy. Presence of SIBO after 4-6 months of cholecystectomy was not significantly different as compared to before cholecystectomy in gallstone patients. However, SIBO was present in 13/49 (26.5 %) late post-cholecystectomy patients with duration of 2-15 years, which was significantly (p<0.05) higher as compared to pre-cholecystectomy and 4-6 months post-cholecystectomy.

Conclusion: This study indicates that longer duration of post-cholecystectomy can lead to delayed OCTT and cause SIBO in gallstone patients. This can be avoided by giving pro-kinetics to post-cholecystectomy patients.

Presidential Posters

Young Investigator Award

PYIA-1

Low T 3 levels correlate with high ferritin levels and mortality in decompensated cirrhosis and in acute-on-chronic liver failure

Rakhi Maiwall 1 , Suman Kumar 2 , S K Sarin 1

1Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India, and 2Department of Hematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India

Background and Aims: We have recently shown that serum ferritin along with hepatic encephalopathy, leukocyte count, acute-on-chronic liver failure (ACLF) grades and CTP score predict early mortality in patients with decompensated cirrhosis (DC). The liver is known to play a very important role in the metabolism of thyroid hormone as it is not only an active site of peripheral deiodination but also governs it’s conjugation, excretion including the synthesis of thyroxine binding globulin. Thus abnormalities in thyroid function are known to correlate with hepatocellular dysfunction but there are no studies evaluating this issue. We therefore aimed to study the thyroid test abnormalities in patients with decompensated cirrhosis and compared it to those with ACLF. We also compared whether these abnormalities correlate with serum ferritin and other predictors of early mortality in these patients.

Patients and Methods: Three hundred and eighteen patients with decompensated cirrhosis and 148 patients with ACLF were included.

Results: Patients of decompensated cirrhosis (257 males, mean age 51 (±13) years and ACLF (109 males, mean age 34 (±5) years were followed for a median of 31 days (1-984) respectively median free T3, free T4 and TSH concentration were 2.3 (IQR 198-2.69) pg/mL, 1.04 (IQR 0.9-1.23) ng/L and 2.47 (IQR 1.28-4.27) μIU/mL respectively in the decompensated cirrhotic group. On the contrary, median (IQR) free T3, free T4 and TSH concentration in patients with ACLF were much lower as compared to patients with decompensated cirrhosis i.e. 1.9 (1.6--2.2; p<0.0001) pg/mL, 0.96 (0.73-1.12; p-0.001) ng/L and 2.1 (0.65-3.5; p=0.01) μIU/mL respectively. Low free T3 was noted in 89 % vs. 64 % (p<0.0001), low T4 in 16 % vs. 4 % (p<0.0001) and low TSH was noted in 18 % vs. 3.5 % (p<0.0001) in patients with ACLF as compared to patients with decompensated cirrhosis respectively. A significant inverse correlation of T3 was noted with predictors of early mortality i.e. MELD (p=0.0004, -0.36) and CTP score (p<0.00001, -0.43), hepatic encephalopathy (p<0.0001, -0.46) and leukocyte counts (p=0.002, -30). Interestingly, low T3 levels also correlated with increasing ferritin (p=0.007, -0.27). Low T3 was also associated with decreased survival in patients with decompensated cirrhosis (log rank p=0.0003), which was not observed for T4 (p=0.5) and TSH levels (p=0.6). On multivariate analysis however low T3 was not a significant predictor of mortality in these patients. Interestingly, serum ferritin showed an inverse correlation both with free T3 (r-0.18, p=0.0120) and with TSH (r-0.234, p=0.03) in patients with ACLF. Also, in these patients a significantly worse survival was noted with low T3 (log rank p=0.005), low T4 (p=0.014) as well as low TSH (p=0.001).

Conclusion: Low T3 levels are frequent in patients with advanced liver disease and correlate with markers of disease severity and outcome, but these abnormalities are more severe in patients with ACLF. It remains elusive whether this occurs as a protective adaptation or as a maladaptive response to the systemic stress and whether restoration of these alterations with thyroid hormones could contribute in recovery of any physiological or metabolic parameters of such critically ill patients with liver disease.

PYIA-2

A brief report on the novel molecular alterations in the ORF 2 capsid gene of hepatitis E virus in patients with acute liver failure in North India

Jayanta Borkakoti 1, 2 , Giasuddin Ahmed 2 , Syed Akhtar Hussain 3 , Arvind Rai 4 , Premashis Kar 1

1PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, University of Delhi, Bahadur Shah Zafar Marg, New Delhi 110 002, India; 2Department of Biotechnology, Gauhati University, National Highway 37, Gopinath Bordoloi Nagar, Jalukbari, Guwahati 781 013, Assam, India, and 3Department of Biotechnology, Jamia Millia Islamia University, Jamia Nagar, New Delhi 110 025, India

Hepatitis E virus (HEV) is evolving as a major global threat to public health including developed countries. We partially sequenced the ORF 2 capsid protein of the HEV genome in patients with acute liver failure including pregnant women in the Northern part of India. Five unique synonymous and 1 non-synonymous substitution along with two novel mutations P259S and S209P in the capsid gene were identified which may be associated with the poor outcome in the patients. Phylogenetic analysis revealed that the isolates belonged to genotype 1 with subtype 1a. The significance of these findings in disease pathogenicity needs to be further determined.

PYIA-3

Clinical and molecular risk factors of antitubercular therapy induced hepatitis

Premashish Kar, Anita Chakrvarty, Suresh Kumar, Shilpa Arora

Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi 110 002, India

Background: The present study is a case control study which aimed at evaluating clinical as well as molecular risk factors for occurrence of antitubercular therapy (ATT) induced hepatitis in Northern Indian population.

Methods: Forty patients of ATT induced hepatitis and 60 pulmonary tuberculosis patients on ATT without liver dysfunction were studied and compared for clinical factors such as age, gender, nutritional status, HBsAg carrier, chronic hepatitis C and HIV infection. Molecular factors i.e. NAT2 acetylator status, GSTT1 and M1 null mutation were also determined in all of the patients in each group and compared.

Results: Mean body weight and serum albumin were significantly lower in the ATT induced hepatitis patients as compared to the control group. No preferential association was observed between age and gender with ATT induced hepatitis. HBsAg carrier (OR- 6.5; p=0.03), HIV infection (OR-5.1; p=0.01), slow acetylator phenotype (OR-3.85; p=0.02), GSTM1 null mutation (OR-2.72; p=0.02) and GSTT1 null mutation (OR 3.12; p=0.02) were found to be positively co-related to ATT induced hepatitis according to the univariate analysis. HBsAg carrier (OR-23.18; p=0.01), HIV infection (OR-16.92; p=0.02), slow acetylator phenotype (OR-70.90; p=0.001), GSTM1 null mutation (OR- 37.03; p=0.002) and GSTT1 null mutation (OR 8.19; p=0.014) were also found to be independently increasing the risk of ATT induced hepatitis using multivariate analysis.

Conclusion: The present study could establish a positive co-relation between malnutrition, HBsAg carrier, HIV infection, NAT2 slow acetylators, GSTM1 null mutation, GSTT1 null mutation and ATT induced hepatitis.

PYIA-4

Celiac disease in women with infertility: A meta-analysis

Prashant Singh , Shubhangi Arora, Suman Lal, Tor A Strand, Govind K Makharia

Department of Medicine, Massachusetts General Hospital, Boston, USA, Department of Medicine, Brigham and Women's Hospital, Boston, USA, Max Healthcare, Sector 29, Gurgaon, Haryana 122 009, India, Medical Services Division, Innlandet Hospital Trust, Lillehammer, Norway, Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India

Background: Celiac disease (CeD) is a systemic disease with manifestations not limited to small intestine. The data on association between CeD and infertility is contradictory. There are no recommendations for the screening of infertile women for CeD. We conducted a meta-analysis of available studies to find out if women with infertility are at higher risk of CeD.

Methods: Literature search was done using the MeSH keywords “CeD” “gluten” and “infertility”. Diagnosis of CeD was based on a positive serology and biopsies showing villous atrophy. Data was extracted about CeD patients in– women with infertility (including unexplained infertility), unexplained infertility and controls. Pooled odds ratio (OR) and prevalence, with 95 % confidence intervals (CI), were calculated.

Results: Of 105 relevant studies, six studies were included for calculation of pooled OR. Four additional studies, where data on controls was not available, were considered for calculation of pooled prevalence of CeD. Women with infertility had 4.6 times higher odds of having CeD in comparison to controls (OR 4.6, 95 % CI 2.2-9.7; p<.001). Similarly, women with unexplained infertility had six times higher odds of having CeD than controls (OR 6, 95 % CI 2.4-14.6). Of 1,084 women with infertility, 26 had CeD indicating a pooled prevalence of CeD to be 2.4 % (95 % CI-1.6, 3.5). Of 623 women with unexplained infertility, 20 had CeD. The pooled prevalence of CeD in women with unexplained infertility was 3.2 (95 % CI 2-4.9).

Conclusions: Women with infertility are at higher risk of CeD and they should be screened for CeD.

PYIA-5

Coagulopathy in cirrhosis: A prospective study to correlate conventional tests of coagulation and bleeding following invasive procedures in cirrhotics

Apurva Shah , Deepak Amarapurkar, Mrudul Dharod, Madhuri Chandnani, Rajiv Baijal, Praveen Kumar, Mayank Jain, Nikhil Patel, Praful Kamani, Nimish Shah, Sandeep Kulkarni, Sonali Gautam, Soham Doshi

Bombay Hospital and Medical Research Centre, 12, Marine Lines, Mumbai 400 020, India

Background: Conventional tests of coagulation which only measure procoagulant factors do not correctly estimate the actual in-vivo hemostatic balance in cirrhosis.

Aims and Methods: This prospective multicentre study was conducted to evaluate safety of various invasive procedures in the presence of abnormal coagulation tests and to correlate various conventional coagulation parameters with clinically significant bleeding in cirrhotics. Three hundred and eighty patients (median age 54 years, 287 males) enrolled in the study, were divided into two groups (A and B), according to presence or absence of abnormal coagulation parameters (defined as INR >1.5 and/or platelet count <50,000/cum).

Results: One hundred and twenty-eight patients (33.68 %) qualified in group A. Alcohol was the predominant etiology of cirrhosis (40 % and 32 % in groups A and B, respectively). The two groups were similar in demographics, laboratory parameters other than tests of coagulation and severity of liver disease. Low risk procedures (abdominal paracentesis most common) were carried out in 47 % and 53 % patients in groups A and B respectively. None of the patients in either group had clinically significant bleeding. Similarly, high risk procedures (central vein cannulation, liver biopsy etc.) were carried out in 14 % and 10 % respectively in 2 groups. Three patients in group A developed clinically significant bleeding, however the difference was statistically non-significant (p=0.061). None of our patients received periprocedural correction of abnormal coagulation parameters with plasma/platelet concentrate.

Conclusion: Deranged conventional coagulation parameters do not predict clinically significant bleeding in cirrhosis. Whenever indicated, any invasive procedure can be safely carried out in patients with cirrhosis without prior correction of coagulation abnormalities.

PYIA-6

The association of HLA-DRB1 allele polymorphism with genetic susceptibility to HBV infections from North India

Vijay Kumar Karra , P K Gumma, R Ruttala, S J Chowdhury, S K Polipalli, Anita Chakravarti, P Kar

Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi 110 002, India

Aim: Human leukocyte antigens (HLA) are highly polymorphic cell surface proteins. Distribution of HLA alleles vary among different racial and ethnic populations. We intended to analyze the relationship between (HLA)-DRB1 alleles and hepatitis B infection.

Materials and Methods: A case-control study was conducted, in which HLA-DRB1 allele frequency was studied in six groups [acute HBV cases 134, chronic hepatitis B 48, HBV related cirrhosis 84, HCC 30, inactive HBV carrier group 20 and 280 healthy controls. HLA-DRB1 alleles were detected by polymerase chain reaction-sequence specific primer (PCR-SSP). Statistical results were analyzed using Fisher’s exact test and p-values were corrected by the Bonferroni correction.

Results: The frequency of HLA-DRB1*0301 allele in groups, persistent HBV infection, chronic hepatitis B, HCC, inactive HBV carrier was markedly lower than that of healthy control group (75.0 %, 66.6 %, 60.0 %, 55.0 % respectively vs. 83.5 %, p< 0.01); the frequency of DRB1*0701/0702 in groups persistent HBV infection, chronic hepatitis B, HBV related cirrhosis was markedly higher than that of healthy control group (48.0 %, 37.5 %, 38.0 %, respectively vs. 16.4 %, p<0.01).

Conclusion: HLA-DRB1*0301, DRB1*1101/1104, DRB1*1301/1302 and DRB1*0901 may be the protective gene, and DRB1*0701/0702 may be the susceptible genes to hepatitis B infection, and that host HLA class II gene is an important factor determining the outcome of HBV infection, which will give some new clues to the study of pathogenesis of chronic hepatitis B.

PYIA-7

CD4+CD25+CD127Low regulatory T cells play predominant anti-tumor suppressive role in hepatitis B virus associated hepatocellular carcinoma

Shreya Sharma 1 , Ritu Khosla 1 , Paul David 1 , Rakhi Maiwall 2 , Archana Rastogi 3 , Ashish Vyas 1 , Dileep Singh 1 , Amrish Sahney 2 , Ankit Bhardwaj 2 , Shiv Kumar Sarin 2 , Nirupama Trehanpati 1

1Departments of Research, 2Hepatology, and 3Pathology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Background: HCC is second leading cause of cancer death worldwide and HBV is one of the commonest causes. Tregs are strong immunomodulators, likely to play major role in HCC development. HBV infection induces Tregs expansion. We investigated expression and functionality of CD4+CD25+CD127-veFoxP3+Tregs in HBV-HCC and non-HBV-HCC.

Patients and Methods: Patients HBV-HCC (n=17), non-HBV-HCC (n=22; NASH=16, ALD=6) and chronic HBV infection (CHBV; n=10), were recruited for study. Whole blood immunophenoty** was done by multicolor flow cytometry. T regulatory cells and functionality was checked by in vitro suppression assay using CD4+CD25+CD127low Tregs. Expression of FoxP3, IL-10, PD1, TGF-β and Notch in Tregs and liver explants was analyzed by flow cytometry, IHC and qRT-PCR.

Results: CD4+CD25+hi and Foxp3 expression in CD4+CD25+hiCD127low was significantly increased (p=0.04, p=0.007) in HBV-HCC compared to non-HBV-HCC and CHBV patients. HBV-HCC also showed high IL-10 and TGF-β secreting CD4+CD25+hiTregs with increased in vitro suppressive ability. The PD1 expression in CD4+CD25+hi was significantly decreased in the HBV-HCC than non-HBV-HCC. In HBV-HCC, levels of AFP were significantly high (median 941, range 2-727940) than non (median 13.5, range 2-18,900). In HBV-HCC, patients with high AFP (range; 3982-727940 ng/mL) showed positive correlation with Foxp3 expression in CD4+CD25+hi CD127low (r=0.857, p=0.014). Reduced PD1 expression in HBV-HCC also had negative correlation with FOXP3 in CD4+CD25+hi CD127low (r=-0.78, p=0.04). However, AFP levels in non-HBV-HCC showed negative correlation with (R=-0.67, p=0.005) with CD4+CD25+hi Tregs.

Conclusions: Our results demonstrates that CD4+CD25+hi Tregs from HBV-HCC patients have decreased PD1 expression, resulting in higher IL-10 and TGF-β secretion. Increased suppressive ability of Tregs in HBV-HCC confers increased anti-tumor suppressive response than non-HBV-HCC. Modulation of Tregs and PD1 may serve as therapeutic targets.

PYIA-8

Cirrhotic circulating endothelial progenitor cells enhance angiogenesis and liver fibrosis in bile duct-ligated rats

Mohsin Hasan 1 , Dinesh Tripathi 1 , Skand Gupta 2 , Vaibhav Dixit 2 , Hamda Sidiqqui 2 , Chaggan Bihari 1 , Savneet Kaur 2 , Shiv K Sarin 1

1Institute of Liver and Hepatobiliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India, and 2Gautam Buddha University, Greater Noida, Gautam Buddha Nagar, Uttar Pradesh 201 312, India

Aim: The current study we evaluated the effect of cirrhotic and control EPCs on hepatic angiogenesis and fibrosis in vivo. The study also investigated the in vitro interaction of these cells with resident hepatic stellate cells (HSCs)

Methodology: Cirrhotic animal models were prepared by identifying and ligating the bile duct. Circulating EPCs isolated from cirrhotic and healthy human blood were cultured ex vivo and transplanted in different groups of BDL rats via tail vein two weeks after the ligation. The cells were given thrice a week for two weeks. The untreated group of BDL rats received only saline. Liver functions and fibrosis was evaluated by histopathology of the liver tissues in untreated, control and cirrhotic EPC-treated rats. The expression of important angiogenic markers, VEGF and CD31, fibrogenic markers, alpha-SMA and TGF-beta and regeneration markers, PCNA and HGF was studied in different BDL rats by western blotting and immunohistochemistry. For the in vitro studies, HSCs were co-cultured with conditioned media (CM) obtained from control and cirrhotic EPCs. The proliferation of HSCs was analyzed by bromodeoxyuridine assays and the levels of an important angiogenic factor secreted by HSCs, vascular endothelial growth factor (VEGF) was evaluated by ELISA in presence of EPC-CM from patients and controls.

Results: Fibrosis studies revealed an increase of fibrosis (from grade 2 to 4) in cirrhotic-EPC-treated rats as compared to healthy EPC-treated and saline-treated rats. Immunohistochemical and western blot data showed an enhancement of both fibrosis and angiogensis markers, alpha-SMA and CD31 in cirrhotic EPC-treated rats as compared to healthy EPC-treated and saline-treated rats (p<0.01). With respect to the regeneration markers, maximum PCNA positivity was obtained in control EPC-treated BDL rats while HGF was more in both control and cirrhotic EPC-treated rats in comparison to saline-treated rats. There was however no significant differences in the liver functions among different groups of BDL rats. In the in vitro studies, HSCs co-cultured with EPC-CM from cirrhotic patients showed significantly increased proliferation in comparison to that observed in HSCs alone (p<0.05). However, VEGF levels in HSCs did not show a significant change in presence of EPC-CM from the patients and controls.

Conclusion: The study suggests that EPCs contribute to in vivo angiogenesis in the injured liver and that cirrhotic EPCs have enhanced angiogenic and fibrotic functions as compared to the healthy EPCs.

PYIA-9

Probiotic prevents the development of portal hypertension in an endotoxin induced portal hypertension model

Nidhi Chaudhary , Rashmi Babbar, M Fahim, S K Sarin

Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: Probiotics and antibiotics have been suggested to influence splanchnic vasodilatation and alter portal hemodynamic through modulation of gut microbiota. We studied the mechanisms and effects of probiotic and antibiotic treatment on development of portal hypertension (PHT) and compared their efficacy.

Animals and Methods: A model of endotoxin induced portal hypertension (EIPHT) was developed in rabbits by injecting lipopolysaccharide (4 mg/mL/1 kg body weight) through an indwelling cannula into the gastrosplenic vein. Such animals (n=62) were divided into three groups; endotoxin alone EIPHT, probiotic (VSL#3,250 billion bacteria/d for two month) EIPHT+VSL#3 and norflox (60 mg/d) EIPHT+norflox. Portal hemodynamic studies and mRNA expression of TLR4/CD14 and proinflammatory cytokines by real-time-PCR were performed baseline 1 and 6 months.

Result: No significant hepatic parenchymal dysfunction was seen in experiment groups. Endotoxin treated animals showed increased portal pressure (>10 mmHg) as compared to their sham group (p<0.05) at one and six month (17.6±1.12 and 18.3±1.17 mmHg). Probiotic (12.21±1.12 and 14.41±1.71 mmHg) and norfloxcin (13.47±0.76 and 16.07±1.4 mmHg) significantly reduced the portal pressure compared to endotoxin group at one and six month. Norflox compared to probiotic showed higher portal pressure. Expression of TLR4 (0.452±0.575 vs. 2.217±1.65) and CD14 (0.508±0.375 vs. 1.873±1.25) was (p<0.05) lower in EIPHT+VSL#3 animals compared to endotoxin EIPHT. Probiotic also showed reduced (p<0.05) expressions of proinflammatory cytokine such as TNF-α (1.083±1.012 vs. 3.671±2.60), IFNγ (1.237±0.840 vs. 3.605±2.48) and IL6 (0.319±0.485 vs. 2.82±1.94) as compared to endotoxin treated group. Norfloxin showed reduced expression of TLR4 (0.066±0.91)/CD14 (0.921±1.24), TNF-α (1.725±1.43) and IFNγ (1.781±1.697) as compare to EIPHT but not significant.

Conclusion: Our results showed that orally administered probiotics are more effective than norfloxacin in protecting gut microflora against LPS-induced portal hypertension. We showed that the induced expression of TLR4/CD14 and proinflammatory cytokine after LPS mediated portal hypertension can be abrogated by probiotic VSL#3 therapy and ameliorate development of portal hypertension.

PYIA-10

Impaired neutrophil function aggravates liver injury and correlates with clinical severity indices in acute-on-chronic liver failure

Arshi Khanam 1 , Nirupma Trehanpati 1* , Peggy Riese 2 , Archana Rastogi 3 , Carlos Alberto Guzman 2 , Shiv Kumar Sarin 1, 4*

1Department of Research, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India; 2Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany; 3Departments of Histopathology, and 4Hepatology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Impaired neutrophil function has been demonstrated in acute liver failure and serves as a biomarker involved in organ dysfunction and increase susceptibility to sepsis. However, its role in acute-on-chronic liver failure (ACLF) remains completely unknown. We assessed phenotypic and functional alterations of neutrophils and their contribution in hepatic injury in 17 hepatitis B virus-related ACLF (HBV-ACLF), 19 alcohol–related ACLF (alcoholic-ACLF), and 42 chronic hepatitis B (CHB) patients in comparison to 18 healthy controls (HC). Neutrophil phagocytic activity (NPA) was determined by the uptake of opsonized E. coli and reactive oxygen species (ROS) production with or without E.coli stimulation. CXCR-1 and CXCR-2 expression was analyzed by flowcytometry, immunohistochemistry (IHC) and qRT-PCR. Percentage of neutrophils was higher in both HBV and alcoholic-ACLF patients than CHB and HC (Table). Contrarily, NPA was significantly impaired in ACLF along with significant increase in ROS. Flowcytometry and IHC showed up-regulated CXCR-1 and 2 in ACLF. In ACLF, intrahepatic CXCR-1 and 2 gene expression was higher more than 6 fold (p<0.00) with a significant increase in pro-inflammatory cytokines (IL-6, IL-17, IL-23, CXCL-8, CCL-20 and GM-CSF). Role of neutrophils in hepatic injury was determined by co-culturing of LPS stimulated neutrophils or their supernatant with HepG2 cells. As compared to controls, activated neutrophils from ACLF significantly induced early apoptosis (p<0.04, 0.05) and necrosis (p<0.00, 0.00) of HepG2 cells by direct contact as well as cytokine/ROS dependent mechanisms.

Conclusions: ACLF patients have increased frequency of neutrophils, with high expression of migration receptors CXCR1/CXCR2. These activated neutrophils produce high ROS but have impaired phagocytic activity with high pro-inflammatory cytokine propagating hepatic injury and liver failure. Neutrophil functional markers represent a powerful tool for drug targets and clinical management of ACLF patients.

Esophagus

E-01

Study of etiological profile of dysphagia on upper gastrointestinal endoscopy in tertiary care center

G Swathi , P Shravan Kumar, M Umadevi, M Ramanna

Department of Gastroenterology, Gandhi Medical College and Hospital, Musheerabad, Secunderabad 500 003, India

Aim: Aim of our study is to evaluate etiological profile of dysphagia in tertiary care center.

Methods: Adult patients (±18 years) presenting with dysphagia were included. The study included the patients presenting with dysphagia from June 2012 to May 2014. All patients underwent upper gastrointestinal endoscopy and relevant investigations.

Results: Out of 226 patients, 120 males (53 %) and 106 females (47 %). The patients were between ages of 18-80 years. Severe esophagitis secondary to gastroesophageal reflux disease was present in 44 cases (20 %). Esophageal cancer present in 40 cases (18 %). Postcorrosive esophageal stricture in 38 cases (17 %) of which 71 % are males and 29 % females, normal study in 38 cases (17 %) out of which 73 % are above 45 years of age. Postcricoid web in 21 cases (9 %) of which all are females, achalasia in 15 cases (7 %), peptic stricture in 10 cases (4 %), esophageal candidiasis is present in 10 cases (4 %), postradiotherapy stricture in 8 cases (3 %), Schatzki ring in 2 cases (1 %).

Conclusion: Non obstructive mucosal lesion causing dysphagia was found to be the most common cause of dysphagia followed by esophageal carcinoma in this study.

E-02

Etiological spectrum of motor dysphagia as per Chicago classification-Experience at a tertiary center in Central India

Mayank Jain , Sandip Ware, Amit Bundiwal, Shohini Sircar, Ajay K Jain

Department of Gastroenterology Choithram Hospital and Research Centre, 14, Manik Bagh Road, Indore 452 014, India

Aims and Objectives: To analyze the demographic, symptomatic and manometric profile of patients with motor dysphagia at a tertiary referral centre in Central India using the recent Chicago classification.

Methods: This is a retrospective analysis of data. The records of all patients who underwent high resolution esophageal manometry for suspected motor dysphagia from March 2012 to March 2014 were analyzed.

Results: A total of 70 patients formed the study group. The mean age was 43.1 years and thirty-nine were males. The major symptoms reported were: dysphagia for solids (90 %), dysphagia for liquids (75.7 %), regurgitation (47.1 %), chest pain (31.4 %), weight loss (31.4 %) and respiratory complaints (5 %). The etiological causes for motor dysphagia, based on high resolution manometry findings, were as follows: achalsia cardia (40), distal esophageal spasm (6), hypertensive peristalsis (5), scleroderma esophagus (5), nonspecific dysmotility (5), hypotensive lower esophageal sphincter (4), frequently failed peristalsis (1), weak peristalsis with small (1), large defects (2) and cricopharangeal achalasia (1). Type 1 achalsia was the commonest form (21/40) followed by type 2 (15/40) and type 3 (4/40) variants.

Conclusion: Majority of patients with motor dysphagia present with dysphagia for solids and liquids. Regurgitation, chest pain and weight loss are seen in one third of the patients. Achalsia cardia is the commonest cause of motor dysphagia. Type 1 achalsia was the most common variant of achalsia in our study.

E-03

Analysis of types of esophageal strictures and response to endoscopic dilatation

Roji Ray , T M Ramachandran, Varghese Thomas

Department of Gastroenterology, Government Medical College, Calicut 673 008, India

Aims: To study the profile of esophageal strictures and the response to endoscopic stricture dilatation.

Methods: Patients with esophageal strictures who underwent dilatation using Savary-Gilliard dilators were included in the study. The most likely etiology of stricture was identified. Length and location of strictures were determined radiologically and endoscopically. Number of sessions and response to dilatation were noted. Factors predicting response to esophageal stricture dilatation were assessed.

Results: Forty-five patients were studied; 21 (46.7 %) were males. Mean age was 55.2±15.4 years. There were 15 (33.3 %) peptic strictures, 11 (24.4 %) corrosive, 16 (35.6 %) postradiation, 2 (4.4 %) malignant and 1 (2.2 %) anastomotic stricture. Corrosive strictures were more in females (n=7; 63.6 %). Eight had multiple strictures. Peptic strictures had length less than 5 cm and involved lower and midesophagus in 93.4 % of patients while all corrosive strictures were in upper and midesophagus. Fifty percent of postradiation strictures involved midesophagus. Twenty-nine (64.4 %) had adequate dilatation. Peptic strictures patients had symptomatic relief with 2.6±1.2 dilatation sessions compared to corrosive and postradiation groups who required 4.0±2.4 and 3.5±1.7 sessions respectively. Those with peptic stricture had better treatment response with mean dysphagia score of 1.1±0.7 after dilatation compared to corrosive and postradiation groups (2.1±0.7 and 2.1±0.5 respectively).

Conclusion: Endoscopic dilatation is an effective and safe treatment for esophageal strictures. Corrosive strictures were more common in young females, most were multiple and located in upper or midesophagus. Peptic strictures were short and located in distal esophagus. Peptic strictures had better response to dilatation and required fewer sessions for symptomatic relief.

E-04

Dexlansoprazole is safe and effective in Indian gastroesophageal reflux disease patients

Shobna Bhatia , 1 Unmesh Takalkar, 2 Sandeep Nijhawan, 3 Vijay Sharma, 4 Sunil Gupta, 5 Sandeep Kansal, 6 Shrish Bhatnagar, 7 B Ravi Shankar, 8 Mahendra Parmar, 9 Ramesh Satarkar, 10 Sanjay Salunkhe, 11 Punit Mehrotra, 12 S D Wagle, 13 Tejas Modi, 1 Jaydeep Gogtay 14

1K E M Hospital, Mumbai; 2Kodlikeri Memorial Hospital, Aurangabad; 3S M S Hospital, Jaipur; 4Vijay Sharma Gastroenterology Clinic, Jaipur; 5Global Gastro and Liver Centre, Jaipur; 6Civil Hospital, Surat; 7Rajajipuram Hospital and Maternity Centre, Lucknow; 8Yashoda Hospital, Hyderabad; 9Government Medical College and S S G Hospital, Vadodra; 10Satarkar Gastroenterology Centre, Aurangabad; 11Noble Hospital, Pune; 12Lucknow Gastroenterology and Gynecology Centre, Lucknow; 13K E M Hospital, Pune; 14Medical Services, Cipla Ltd, Mumbai, India

Background: Dexlansoprazole, an enantiomer of lansoprazole, is a novel modified release (MR) formulation, designed to overcome the limitations of currently available PPIs.

Aim: We compared the efficacy and safety of dexlansoprazole and lansoprazole in Indian gastroesophageal reflux disease (GERD) patients.

Methods: Patients with GERD symptoms were enrolled into a multicentre, double blind, randomized, phase-III trial, and stratified after endoscopy into two groups, viz. erosive esophagitis (EE) and nonerosive reflux disease (NERD). Patients with EE received either dexlansoprazole 60 mg or lansoprazole 30 mg, and those with NERD received dexlansoprazole 30 mg or lansoprazole 15 mg for 8 weeks each. Primary end-point was the mean change in Gastroesophageal Reflux Disease Symptoms Assessment Scale (GSAS) scores from baseline to week 8 of treatment. Ethics committee approval was taken at all study sites, and the study was conducted as per ICH-GCP guidelines.

Results: Overall 260 consenting patients (mean age 38.5 [11.3] years; 72 % men) were included. Dexlansoprazole was as effective as lansoprazole for the primary end-point  (Table). During the study period, patients treated with dexlansoprazole experienced relief from nocturnal heartburn on 96 % of the median nights compared to 93 % with lansoprazole group. Both the doses (30 mg and 60 mg) of dexlansoprazole were well tolerated and no unexpected safety events were identified.

Conclusion: Dexlansoprazole MR was as safe and effective as lansoprazole for the management of EE and NERD. In patients experiencing night-time symptoms, dexlansoprazole may be effective in relieving the nocturnal symptoms.

Acknowledgment: The study was supported by an educational grant from Cipla, India.

Table: Results

Parameters

Dexlansoprazole (n=131)

Lansoprazole (n=129)

GSAS Score

  

Baseline

8.3 (5.0)

8.2 (5.4)

Week 8

3.9 (4.4)

3.4 (4.1)

Change from baseline

-4.4 (4.8)

-4.9 (4.7)

Percentage of heartburn-free days

  

Baseline

7.1 (12.8)

6.6 (12.4)

Week 8

58.6 (41.4)

54.8 (43.7)

Percentage of nights without heartburn

  

Baseline

27.6 (34.4)

29.0 (35.4)

Week 8

69.3 (39.0)

63.2 (42.7)

All values are as mean (SD)

E-05

A study on association of esophageal malignancy in postcricoid web

C Vaishnavi Priyaa , K Muthukumaran, G Ramkumar, R Balamurali, T Rajkumar Solomon, P Ganesh

Department of Digestive Health and Diseases, Kilpauk Medical College and Hospital, Chennai 600 010, India

Aim: Plummer–Vinson syndrome (PVS), has an association with malignancies of oral cavity, cricopharynx and esophagus. This is a single centre study to establish the significant association of esophageal malignancy in postcricoid web, epidemiology, and anatomical distribution.

Materials and Methods: An observational study was done at our centre, from July 2012 to July 2014 for 2 years. Seventy-three cases of postcricoid web were dilated and assessed for coexisting esophageal malignancies. The mean age at presentation was 46 years (range 18-70 years).

Results: Total postcricoid web dilated were 73 (8 male/65 female) and 9 cases (12 %) (7 female/2 male) had associated esophageal malignancy. Upper esophagus-1, middle esophagus-1, lower esophagus growth-7 (78 %). One female (1.5 %) had growth stomach. Two (1.5 %) had stricture lower esophagus (1-malignant stricture and 1 benign stricture). Two cases had cricopharyngeal growth in patient with previously dilated postcricoid web (3 %) (1 male/1 female).

Conclusion: There was incidence of 13.6 %, esophageal malignancy in postcricoid web at our centre. Predominantly lower esophagus (80 %) was involved. Overall 90 % were females with associated oropharyngeal, esophageal and gastric malignancies. With an increased risk of squamous cell carcinoma of the pharynx and the esophagus, the patients should be followed closely. A surveillance upper gastrointestinal endoscopy may be recommended every year, even though the effectiveness of this recommendation is not definitively confirmed.

E-06

Endoscopic profile of dysphagia - A prospective study

Nitin Gaikwad , Sudhir Gupta. Amol Samarth, Neeraj Sawalakhe

Department of Gastroenterology, Government Medical College and Super Specialty Hospital (SSH), Nagpur 400 009, India

Introduction: Dysphagia causes significant morbidity and mortality especially in elderly. Our aim was to analyze the endoscopic features and histopathologic correlation in the patients presented with dysphagia.

Material and Method: It was a prospective study of 6 months duration at our institute from January 2014 to June 2014. During this period, 1,392 patients underwent upper gastrointestinal (GI) endoscopy. One hundred and sixty-five (11.85 %) had dysphagia. Twelve had normal upper GI endoscopy and were excluded from analysis. Data of 153 patients (10.99 %) was analyzed.

Results: Mean age of the patients was 54±2 years. M:F ratio was 2.06:1. Endoscopic feature were assessed: 33 (21.56 %) had esophageal malignancy. 18/33 (54.54 %) upper, 9/33 (27.27 %) mid and 6/33 (18.18 %) patients had lower esophageal involvement: (among these gastroesophageal junction malignancy attributed to 8 (24.24 %). Severe GERD (LA grade D esophagitis) was present in 20 (13.07 %). Peptic stricture in 13 (8.49 %), Barrett's  esophagus in 8 (5.22 %), midesophageal ulcer in 11 (7.18 %) patients. Candidial esophagitis in 10 (6.53 %). Corrosive injury in 4 (2.61 %), achalasia in 7 (4.57 %) patients. Esophageal subepithelial lesions were seen in 9 (5.88 %). Midesophageal diverticulum in 5 (3.26 %), foreign body in 2 (1.30 %), tracheoesophageal fistula in 3 (1.96 %), eosinophilic esophagitis seen in 8 (5.27 %). Histopathology revealed squamous cell carcinoma in 26 (78.27 %) and adenocarcinoma 7 (21.21 %) which correlates with our endoscopic findings. Endoscopic ultrasound was performed in selective patients.

Conclusion: Dysphagia has varied etiology. Among all, most common cause is malignancy (squamous cell) in central India.

E-07

Severity of esophageal carcinoma and it correlation with expression levels of O6-methylguanine-DNAmethyltransferase (MGMT) and Runt-related transcription factor 3 (RUNX3) genes in North Eastern region of India

Sngdha Saikia

Department of Biological Science, Gauhati University, Guwahati 14, Assam, India

Introduction and Aim: Kamrup district of Assam in North Eastern India has the highest incidence of esophageal cancer. The association of DNA repair gene MGMT and tumor suppressor RUNX3 expressions in esophageal carcinoma patients have been explored in this study.

Methodology: Grade of dysphagia was classified as described by Blazeby et al. Total RNA were isolated from blood by trizol method and cDNA were synthesized (Invitrogen). The quantification of RUNX3 and MGMT expression was done by QPCR using Syber-green mastermix (Invitrogen) using Î2-actin a internal control.

Result: Fifty-six cases of esophageal carcinoma were included in the study with male: female ratio of 5:3 and mean age in males and females being 61.4±8.52 yrs and 54±13.23 yrs respectively. Histopathology classified 6 patients (10.71 %) of the total as adenocarcinoma and 50 patients (89.28 %) as squamous cell carcinoma. Expression of RUNX3 in grade 1, 2, 3 and 4 dysphagia were 0.3±0.27, 1.1±1.4, 1.43±1.5 and 1.8±2.9 fold respectively. The fold change in MGMT expression were 0.3±0.01, 0.04±0.03, 4.5±9.9, 4.8±16.8 in dysphagia grade 1, 2, 3 and 4 respectively.

Conclusion: There is increment upregulation in the expression of RUNX3 at transcript level among different grade of dysphagia. Whereas other study has reported no expression of RUNX3 in gastric cancer (Li et al. 2002). The high level of MGMT expression in advanced stages of esophageal cancer may avoid the mutagenic and carcinogenic effect of DNA damage.

E-08

Transnasal dilatation of upper aero-digestive tract lesion

P Shanija , Rathnakar Kini, Kani Sheik, K Prem Kumar, T Pugazhendhi, Mohammed Ali

Department of Medical Gastroenterology, Madras Medical College, Rajiv Gandhi Government General Hospital, Chennai 600 003, India

Background: Primary aim of esophageal dilatation is to alleviate symptoms and maintenance of nutrition. Patients with oropharyngeal malignancy with trismus, laryngeal growth and upper esophageal lesion involving postcricoid area, the transoral technique of esophageal dilatation may be difficult.

Aim of the Study: To evaluate clinical profile, efficacy of procedure, procedure related complications in patients undergoing transnasal bougie dilatation of upper aero-digestive tract lesion.

Method: Design: Retrospective and prospective study.

Patients: All patients undergoing transnasal bougie dilatation of upper aero-digestive tract lesion from January 2014 to till date included.

Results: Forty transnasal dilatation were performed in 36 patients using Savary-Gillard dilators ranging from 5 mm to 12.8 mm under fluoroscopy over the guide wire. Mean age of cohort was 50.7 years (range 20-94 years). Twenty-two were male (61.11 %). All the procedures were done as unsedated as inpatients. Twenty-three (63.89 %) patients had esophageal growth. Ten patients (27.7 %) had history of head and neck radiation therapy. Two patients had post pharyngocoloplasty anastomotic stricture done for corrosive injury. Two patients had Ca larynx extended to postcricoid area. The upper esophageal sphincter was the most dilatation site (86.11 %) followed midesophagus (8.33 %) and then lower esophagus (5.55 %). Success rate was 100 %. Twenty-two patients had undergone nasogastric tube insertion following dilatation. There were no clinically significant procedure related complications.

Conclusion: Transnasal bougie dilatation of upper aero-digestive tract lesion is technically easy and safe. NG tube can be rail roaded over the guide wire after the procedure.

E-09

Peroral endoscopic myotomy for achalasia cardia, a single tertiary care experience from India

Sandeep Davavala , Amol Bapaye, Nachiket Dubale, Rajendra Pujari, Suhas Date, VinayThorat

Department of Digestive Diseases and Endoscopy, Deenanath Mangeshkar Hospital and Research Center, Erandawne, Pune 411 004, India

Background and Aim: Treatment for achalasia cardia includes endoscopic (balloon dilatation/botulinum injection) or surgical Heller’s myotomy. Peroral endoscopic myotomy (POEM) is an upcoming modality. This study reports preliminary results of POEM in patients suffering from achalasia cardia.

Materials and Methods: Patients with achalasia cardia confirmed on endoscopy (EGD), high-resolution manometry (HRM) and barium swallow and undergoing POEM were included. Associated comorbidities and previous treatments for achalasia were recorded. Eckhardt score (ES) was recorded before the procedure. Procedure time, technical success and complications were noted. Follow up was by EGD, with or without HRM and post procedure ES at 4 weeks.

Results: Twenty-five patients were enrolled, mean age group (39.9 years) with females (14). Achalasia type: I–5, I–15, not done - 5. Significant comorbidities: 6/25 (24 %). Categories: naïve patients (n-15), previous therapies–Heller’s myotomy (n-2), botulinum injection – (n-1) and balloon dilatation – (n-7). Mean symptom duration: 24-420 weeks. Mean pre-procedure ES–6.5; mean LES pressure 39.9 mmHg (range–17-74 mmHg). Mean procedure duration (minutes) was 187.5 (60 – 330), clinical success (100 %) and no major complications encountered. Technical difficulties in 5/25 (20 %) patients. On follow up (mean 6 months) ES was 1.5 (p=0.001) and mean LES pressure 12.88 (p=0.018). Relief in dysphagia was (100 %) and occasional heartburn in–8/25 (32 %).

Conclusions: POEM is safe and effective treatment for achalasia cardia. It is effective in treating naïve, previously treated patients and also in those with comorbid illness that may preclude surgical treatment.

E-10

Association of polymorphism in heat shock proteins A1B and A1L (HOM) as risk factors for esophageal carcinoma in Assam

Snigdha Saikia 1, 2 , Prajjalendra Barooah 1,2 , Mallika Bhattacharyya 2 , Bhabadev Goswami 2 , Subhash Medhi 1

1Department of Biological Science, Gauhati University, National Highway 37, Gopinath Bordoloi Nagar, Jalukbari, Guwahati, Assam 781 013, India and 2Department of Gastroenterology, Gauhati Medical College, GMCH Complex, GMCH Road, Bhangagarh, Guwahati, Assam 781 032, India

Aim: Kamrup district of Assam has the highest incidence of esophageal cancer. The polymorphism in heat shock proteins A1B and A1L (HOM) and other risk factors for esophageal carcinoma have been explored in this study.

Methodology: The study include esophageal cancer patients attending general OPD and ward of Gauhati Medical College. The patients were diagnosed based on endoscopy findings and histopathology study, genomic DNA were isolated from whole blood by phenol-chloroform method. PCR-RFLP analysis was done for A1B and A1L genes.

Result: A total of 78 cases and 50 healthy controls were included in this study with, male to female ratio of 5:3, mean age 61.4±8.52. Clinicopathological evaluation showed 83.33 % has squamous carcinoma and 16.66 % were adenocarcinoma. Dysphagia grade 4 (41.02 %) and 5 (35 %) were observed by endoscopic and hispathological evaluation. The frequency of A1B gene (p value=0.00) and allelic frequency p=0.00; OR=26 were significant. The heterozygous genomic variants of A1B and A1L gene with p=0.03, chi-square=4.27 OR=0.3 were significant. Among all the risk factors, betel quid, tobacco, smoking has significant correlation between control and cases.

Conclusion: The present study provides marked evidence that functional heterozygous polymorphism of A1B gene may contribute to higher risk of esophageal cancer. Betel quid consumption has been found to be highly significant risk factor, followed by smoking and tobacco chewing. However, one of the limitations of this study is the limited sample size and only preliminary indications can be deduced.

E-11

Coexistence of malignancy in patient with Plummer-Vinson syndrome

Harish Kumar Yedla , M G Srinivas, K R Thankappan

Department of Medical Gastroenterology, Narayana Medical College, Chinthareddypalem, Nellore 524 002, India

Background: Plummer-Vinson syndrome is a premalignant condition for postcricoid carcinoma. Incidence of other malignancies in Plummer-Vinson syndrome is not known.

Methods: It was a retrospective study done in Department of Medical Gastroenterology between June 2012 to 2014. All the patients with dysphagia, anemia, esophageal web were included in the study. All the patients underwent wire guided serial SG dilatations. After dilatation repeat endoscopy done to check for adequacy of dilatation and for complications. Some patients showed growth distal to dilatation were biopsied.

Results: All the patient who were undergone dilatations were females in middle age. Out of 45 patients 4 (8.8 %) showed growth at other than dilatation site. One patient at upper 1/3 rd of esophagus, two patients at lower 1/3 rd of the esophagus and one patient showed growth extending from gastroesophageal junction to antrum.

Conclusions: Plummer-Vinson syndrome is a premalignant condition for esophageal squmaous cell carcinoma. In our study 8.8 % of patients showed malignancy at sites away from web. One patient showed gastric malignancy.

E-12

Clinicopathological audit on esophageal cancer

K Senthamizh Selvan

Department of Medical Gastroenterology, Madras Medical College, Rajiv Gandhi Government General Hospital, Chennai 600 003, India

Background: Esophageal cancer is one of the most lethal human malignancies worldwide. The two most common histological types are squamous cell carcinoma and adenocarcinoma. The former involves upper and midesophagus whereas the latter involves lower esophagus and esophagogastric junction. Squamous cell carcinoma is most common worldwide however recently, there is an increasing trend in adenocarcinoma. Our study aims to compute pathoepidemiology of esophageal cancers in our setup.

Materials and Methods: We conducted a hospital based retrospective analysis of our data, compiled over five years (2010-2014). A total of 270 cases of biopsy proven malignancy of esophagus and esophagogastric junction were analyzed by statistical software.

Results: The mean age of our study population was 54.5 years, male:female ratio of 2.3:1, most common presenting complaints were dysphagia (73 %) followed by dyspepsia (14 %) in both males and females. Most common site of esophagus involved was midesophagus. Esophagogastric junction was involved in 32 cases. Histology showed squamous cell carcinoma in 76 %, adenocarcinoma in 21 % and poorly differentiated carcinoma in 3 %. About 46 % of cases were alcoholics and 31 % of cases were smokers. Tracheoesophageal fistula was present in 17 cases. Synchronous cancers were present in 4 cases (distal esophagus in 1 case and stomach in 3 cases).

Conclusion: Squamous cell carcinoma is still the most common histological type in our setup and midesophagus being the most common site.

STOMACH ( H. pylori )

STH-01

Differentially localized survivin and STAT3 pools as markers of gastric cancer progression

Arvind Pandey 1,2 , Satyendra Chandra Tripathi 3 , Ravi Kant Kumar 4 , Shirish Shukla 1 , Sutapa Mahata 1 , Kanchan Vishnoi 1 , Sri Prakash Misra 4 , Vatsala Misra 5 , Manisha Dwivedi 4 , Alok C Bharti 1

1Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICMR), Noida, India, 2Center for Biotechnology, University of Allahabad, Allahabad, India, and 3UT MD Anderson Cancer Center, Clinical Cancer Prevention-Research, Houston, Texas, US, 4Departments of Gastroenterology and 5Pathology, Moti Lal Nehru Medical College, Allahabad 211 001, India

Aberrantly expressed and activated STAT3 and its downstream gene survivin are emerging as important mediators of chemoresistance, cell survival, metastasis and shown to be associated with cancer prognosis. However, their clinical utility as markers of tumor progression is yet to be established. Recent observations suggest differentially expressed and preferentially localized survivin in tumor cells may be attributed with distinct cellular functions. To understand the expression dynamics of STAT3-survivin loop in different stages of gastric cancer progression, we analyzed 156 tissues (61 normal, 30 precancer and 65 adenocarcinoma) from histopathologically-confirmed gastric endoscopic biopsies. The expression and sub-cellular localization of survivin, STAT3 and pSTAT3 revealed moderate but primarily cytoplasmic survivin in majority of precancer tissues of intestinal metaplasia and dysplasia. In contrast, survivin was highly overexpressed and was detected in both cytoplasm and nucleus of cancer tissues from diffuse and intestinal gastric adenocarcinoma lesions. Survivin positivity was found strongly associated with STAT3 and pSTAT3 positivity. The habits of tobacco or alcoholism alone or in combination and concurrent H. pylori infection were invariably associated with high Survivin/STAT3/pSTAT3 positivity. Marker analysis of survivin, STAT3 and pSTAT3 expression in different subcellular pools among different gastric tissues demonstrated high AUCs and low cut-off values indicative of their utility as markers. Overall, our study showed increasing frequency of survivin positivity and its upstream regulator STAT3 in gastric cancer cells with increased severity of the lesions. Therefore, assessment of subcellular localization of these proteins in tumor tissues could serve as markers of gastric cancer progression.

STH-02

A clinical trial to evaluate the safety and efficacy of UNIM-701 compound in the treatment of duodenal ulcer and eradication of Helicobacter pylori

M A Raheem Rafeeq 1 , M A Waheed 2 , Avinash Bardia 1 , Md. Aejaz Habeeb 1 , Aleem A Khan 1

1Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500 058, India, and 2Central Research Institute of Unani Medicine Erragadda, Hyderabad 500 038, India

Introduction: The gastric pathogen Helicobacter pylori, has been a major cause of peptic ulcer disease and is an early risk factor for gastric carcinoma. It is the second most common chronic bacterial infection in humans. Eradication of Helicobacter pylori is an important event in overcoming gastric diseases. Many regimens are currently available but none of them could achieve 100 % success in eradication. Therefore the present study was designed to evaluate the efficacy of herbal medicine (UNIM-701) in duodenal ulcer.

Materials and Methods: Eighty-five cases of duodenal ulcer were assessed for the clinical trial (56 males and 29 females) with endoscopically proven duodenal ulcer were subjected to trial (UNIM-701 divided in 2 doses) for a period of eight weeks. H pylori infection was assessed by diagnostic tests, rapid urease, direct smear, and histological exam. Clinical assessment was done every week and repeat endoscopy was performed at the end of the therapy.

Result: Seventy-five patients completed the trial and 10 patients dropped out. H pylori became negative in 56 out of the 75 patients who completed trial according to the protocol. Twenty-eight patients were cured and 39 patients relieved symptomatically whereas 8 patients had no response to the therapy. The drug was well tolerated and there was no complaint of any side effects. These results demonstrate that our compound UNIM-701 exhibits bactericidal activity against H pylori.

Conclusion: This may have potential as new and safe agents for treatment of duodenal gastric diseases.

STH-03

Allelic diversity of the Helicobacter pylori vacuolating cytotoxin gene (vacA) in northern India

Jitendra Kumar Choudhary * , M K Tripathi, S K Jena * , A Ranjan, N Gupta, N Singh, A K Jain, S K Shukla, V K Dixit

Department of Gastroenterology, Institute of Medical Science, Banaras Hindu University, Varanasi 221 005, India and *Department of Hepatology, S C B Medical College, Cuttak 753 007, India

Background: VacA, the vacuolating cytotoxin encoded by vacA gene is an important marker for H pylori virulence. The gene vacA is present in all H pylori strains. Three major polymorphic vacA regions have been identified: the signal region(s), the intermediate region (i) and the middle region (m).

Aim: To analyze allelic diversity of H pylori vacA gene at signal region (s1 and s2), intermediate region (i1 and i2) and middle region (m1 and m2).

Methods: A prospective study was performed on 102 patients with antral gastritis, peptic ulcer disease and gastric carcinoma. All the patients were subjected to antral biopsy for ultra rapid urease test (URUT), DNA isolation and histopathology. Isolated DNA was subjected to polymerase chain reaction for H pylori specific 16SrDNA amplification, vacAs1/s2, vacAm1/m2, and vacAi1/i2 allelic characterization.

Results: The mean age of patients were 46.37 (range 18-87). URUT was positive in 56/102 (54.9 %) samples. Amplification of H pylori specific 16s rDNA was done to confirm H pylori infection. The vacA gene was present in all samples. The frequency of vacA allele type s1/m1/i1 (67.64 %) was higher followed by s1/m2/i1 (24.5 %), s2/m2/i2 (5.88 %) and s1/m2/i2 (1.96 %). Allele type s1/m1/i1 was found to be highly associated with peptic ulcer disease (75 %) and gastric cancer (74.7 %). Whereas distribution of s1/m2/i1 allele was high in gastritis (30.23 %) than gastric cancer (25.92 %) and peptic ulcer disease (15.62 %).

Conclusion: Allele vacAs1/m1/i1 was found to be more prevalent and highly associated with peptic ulcer disease and gastric cancer.

STH-04

Markers of gastric acid secretion (pepsinogens and G-17) and inflammatory response (IL-8) are associated with functional dyspepsia particularly in absence of H pylori infection

Sushil Kumar , Uday C Ghoshal

Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Background: Circulating levels of pepsinogen (PG), gastrin-17 (G-17) are known serological marker of gastric acid secretion; Helicobacter pylori infection is known to alter acid secretion, which may be influenced by pro-inflammatory cytokines (e.g. IL-8) through degree and severity of gastritis. Since altered acid secretion may be associated with functional dyspepsia (FD), we undertook this study.

Methods: Serum levels of PG-I, PG-II, PG-I/PG-II ratio, G-17, IL-8 and anti-H pylori IgG were estimated (ELISA) among 60 subjects each with FD (Rome III criteria and normal endoscopy) and healthy controls (HC).

Result: Age, gender and H pylori sero-positivity (44 [73.3 %] vs. 37 [61.7 %]) were comparable among patients with FD and HC. Serum PG-I (median [range]: 76.1[5.3-199.2] vs. 106.4[29.4-225.0], p=0.040) and PG-I/PG-II (5.6[0.5-66.4] vs. 9.8[1.8-28.8], p=0.005) were lower but serum G-17 (12.1[0.2-42.9] vs. 7.3[0.6-73.3], p=0.045) and IL-8 (55.1[4.2-318.9] vs. 26.3[4.7-277.6], p=0.02) were higher among FD than HC, though PG-II was comparable. FD patients without H pylori infection also had lower serum PG-I (72.9[26.1-192.4] vs. 113.8[29.4-225.0], p=0.003), PG-I/PG-II (5.4[1.0-66.3] vs. 8.4[3.6-28.8], p=0.001) and higher G-17 (17.1[1.9-42.9] vs. 5.0[0.9-73.3], p=0.048) and IL-8 (29.5[8.1-163.9] vs. 18.9[4.7-101.9], p=0.03) levels than HC, though the serum levels were comparable among H pylori sero-positive subjects with FD and HC.

Conclusion: Circulating levels of PG-1, PG-I/PG-II were lower but G-17 and IL-8 were higher among patient with FD than HC, particularly those without H pylori infection, suggesting that acid secretion may be higher among patients with FD without H pylori infection than HC.

Stomach (Non- H pylori )

STN-01

Spectrum of benign gastric outlet obstruction in North India

Sudhir Maharshi , A S Puri, Sanjeev Sachdeva

G B Pant Hospital, New Delhi 110 002, India

Background and Aim: Gastric outlet obstruction (GOO) characterized by complete or incomplete obstruction at antropyloric region or proximal duodenum due to intrinsic mucosal disease, external compression, chronic scarring or fibrosis. There is paucity of data on the spectrum of benign GOO.

Aim: Aim was to study the spectrum of benign GOO with a view to identify the subgroup which would be best amenable to endotherapy.

Methods: Prospective study was conducted at G B Pant Hospital, New Delhi between November 2013 and May 2014. All patients with a clinical diagnosis of benign GOO were consecutively enrolled. Data relating to demography, laboratory parameters, radiological imaging, histology and outcome of endotherapy were analyzed. EMR was done in selective cases to facilitate histological diagnosis.

Results: Thirty patients (age 34.7±16.06 years, BMI 16.8±2.8 kg/m2, 22 males) were studied. Etiology of GOO was peptic ulcer disease in 11 (37 %), gastroduodenal tuberculosis in 6 (20 %), corrosive injury in 5 (17 %), duodenal web in 3 (10 %), chronic pancreatitis in 1 (3 %) and idiopathic in 4 (13 %) patients. Histopathology showed granulomatous inflammation in 6 patients of gastroduodenal tuberculosis. Median number of endoscopic dilatations were 3 (1-6) for peptic ulcer disease, 3 (2-6) corrosive and 2 (1-4) for gastroduodenal tuberculosis. Seven (35 %) patients required surgical treatment of which three patients had duodenal ulcer disease nonresponsive to endotherapy.

Conclusion: Peptic ulcer disease, gastroduodenal tuberculosis and corrosive injury are most common causes of benign GOO in north India. In 4 (13 %) patients no cause of GOO was identified, were grouped as idiopathic. Endotherapy is very successful in patients with gastroduodenal tuberculosis.

STN-02

Berberine and curcumin target chemoresistance through inhibition of survivin and STAT3 in gastric cancer cells

Arvind Pandey 1,2,3 , Sutapa Mahata 1 , Kanchan Vishnoi 1 , Ravi Kant Kumar 3 , Sri Prakash Misra 3 , Vatsala Misra 4 , Manisha Dwivedi 3# , Alok C Bharti 1#

1Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICMR), Noida, India, 2Center for Biotechnology, University of Allahabad, Allahabad, India, and 3Departments of Gastroenterology and 4 Pathology, Moti Lal Nehru Medical College, Allahabad 211 001, India

Purpose: Drug resistance is a major obstacle in the treatment of gastric cancer. Aberrantly expressed survivin and STAT3 signaling have emerged as major determinants of intrinsic chemo-resistance in gastric cancer. Present study was conducted to evaluate the effect of potent herbal derivatives like curcumin, berberine and quercetin that could target STAT3 signaling, on survivin and response to standard chemotherapeutic drug 5-fluorouracil (5-FU) in gastric cancer cells.

Methods: The cytotoxic and inhibitory effect of berberine, curcumin and quercetin alone or in combination with 5-FU was checked by MTT assay and their effect on survivin, STAT3 and pSTAT3 expression was examined by western blotting. Effect of these herbal derivatives on STAT3 DNA binding activity that represent active STAT3, was measured by EMSA.

Results: 5-FU at concentration as high as 50μM could not suppress the levels of survivin and STAT3 and was only partially cytotoxic to gastric cancer cells. Curcumin, berberine and quercetin that could effectively target the levels of active STAT3, were also found to dose-dependently down-regulate the levels of survivin. Berberine was found to have strong anti-survivin property among all other pharmacological agents tested. 5-FU in combination with berberine or curcumin showed a synergistic inhibition of survivin and STAT3 levels that was accompanied by synergistic effect on the loss of cell viability in gastric cancer cells resulting in chemosensitization.

Conclusion: Overall, our data suggest use of berberine and curcumin as adjunct therapeutics to prevent onset of chemoresistance during treatment of gastric malignancies.

STN-03

Quality of life in patients with common causes of dyspepsia: A comparative study

Anurag J Shetty , Shiran Shetty, Girisha Balaraju, C Ganesh Pai

Department of Gastroenterology, Kasturba Medical College, Manipal University, Manipal 576 104, India

Introduction: Dyspepsia is a common cause of morbidity and economic loss in the community and can have a significant impact on the quality of life (QoL).

Material and Methods: Three hundred and nineteen consecutive patients with dyspepsia were classified based on a detailed evaluation including upper gastrointestinal endoscopy to have peptic ulcer (PU), gastric cancer (GC) and idiopathic dyspepsia (ID). Health related QoL was assessed using the EQ (Euro QoL) -5D self-reporting questionnaire in the 5 dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression, and also as an overall visual analogue score (VAS).

Results: PU, GC and ID were seen in 60 (18.8 %), 11 (3.4 %), 248 (77.8 %) respectively. Three hundred and seventeen (99.4 %) reported some problem in at least one dimension of QoL. The frequency of severe problems was significantly different between PU (18; 30 %), GC (5; 45.5 %) and ID (123; 49.6 %; p=0.024). One hundred and ninety-nine (62.4 %) had some problem in their usual activity, severe problems showing significant difference between PU (4; 6.7 %), GC (3; 27.3 %) and ID (17; 6.9 %; p<0.05). Pain and discomfort were significantly different in those with PU (56, 93.3 %), GC (11; 100 %) and ID (246, 99.2 %, p=0.01). Anxiety/depression were significantly different in PU (36, 60 %), GC (3, 27.3 %) and ID (189, 76.2 %; p<0.01). The median (IQR) VAS scores did not differ significantly between the subgroups.

Conclusion: Dyspepsia from different causes frequently impaired QoL. Limitation of usual activities was significantly more common with GC. Anxiety-depression was significantly more frequent in patients with ID, which might be responsible for poor scoring in the dimensions of pain and overall QoL in this subgroup.

STN-04

Esophagogastric junction tumors: Our centre experience

S Shankar , K Muthukumaran, G Ramkumar, R Balamurali, P Ganesh, T Rajkumar Solomon, A Murali

Department of Digestive Health and Diseases, Kilpauk Medical College, Chennai 600 010, India

Aim: To study the incidence and the mode of presentation of esophagogastric junction tumors seen in our tertiary care hospital.

Materials and Methods: Retrospective study of duration 3 years from May 2011 to May 2014. All the patients were subjected for symptom analysis, clinical examination, basic hematological work up, upper GI endoscopy and HPE analysis.

Results: Out of the 60 patients, males were 34 (57 %) and females were 26 (43 %). Mean age in males was 66 years and females was 62.2 years. Symptom presentations were dysphagia 20 (34 %), abdominal pain 12 (20 %), abdominal distension 8 (13 %), loss of appetite 10 (17 %), loss of weight 8 (13 %), UGI bleed 2 (3 %), combinations 4 (7 %). UGI endoscopy showed polypoidal form 8 (13 %), ulcerated form 28 (47 %), stricturous form 14 (23 %), combined form 10 (17 %). Siewert type 1-20 (33 %), Siewert type 2- 8 (14 %), Siewert type 3-32 (53 %). HPE analysis showed adenocarcinoma in 48 patients (80 %) and squamous cell carcinoma in 12 patients (20 %).

Conclusions: This study demonstrates that esophagogastric junction tumors are more common in males. Siewert type 3 accounted for majority of the tumors. Adenocarcinoma was the most common histological type.

STN-05

Functional dyspepsia is associated with GNÎ 2 3 C825T polymorphism: A case-control study

Rajan Singh , Balraj Mittal * , Uday C Ghoshal

Departments of Gastroenterology and *Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Background: Functional dyspepsia (FD) is characterized by epigastric pain, burning, early satiety and postprandial fullness in absence of organic or metabolic causes. Gastrointestinal (GI) motor abnormalities and altered visceral sensation have been considered as major pathophysiological mechanisms involved in FD. G-protein beta-3 subunit gene (GNÎ23), C825T polymorphism alters intracellular signal transduction, which may lead to motor or sensory abnormalities of the GI-tract. Therefore, we evaluated the role of this polymorphism in patients with FD as compared to healthy controls (HC).

Methods: Two hundred and thirty-seven consecutive patients with FD (Rome III) and 250 HC were genotyped for GNÎ23 C825T polymorphism (PCR-RFLP). Patients with FD were sub-classified into epigastric pain syndrome (EPS), postprandial distress syndrome (PDS) and EPS-PDS overlap.

Results: Patients with FD [173 (73 %) male, age 38±12-y] were comparable with HC [195 (78 %) male, age 37±12-y] with respect to age and gender. 26/237 (11 %) had EPS, 55 (23.2 %) PDS and 156 (65.8 %) EPS-PDS overlap. Among 237 patients with FD, TT genotype (associated with increased intracellular signal transduction) of GNÎ23 C825T polymorphism was commoner among patients than HC [26 (11 %) vs. 12 (4.8 %) p=0.014, odds ratio (OR) =2.47, 95 % confidence interval (CI) =1.2-5.1]. However, genotypes distribution was comparable among patients with different subtypes of FD (p=0.80).

Conclusion: TT genotype of GNÎ23 C825T is commoner among patients with FD, suggesting that increased signal transduction associated with this genotype may be important in its pathophysiology.

STN-06

Abdominal pain syndrome

Sangameswaran

Madras Medical College, Chennai 600 003, India

Celiac artery compression syndrome, also median arcuate ligament syndrome, Dunbar syndrome is very rare until we investigate completely. It is characterized by clinical triad of postprandial abdominal pain, weight loss and diarrhea. A high index of suspicion is required diagnose vascular etiology in patients with upper abdominal pain and normal upper gastrointestinal endoscopy to avoid labelling them as functional abdominal pain disorder. We report 2 cases of abdominal pain with normal upper gastrointestinal endoscopy with significant postprandial pain who showed features of celiac artery narrowing as a cause of abdominal pain by CT angiogram which is the gold standard imaging modality.

STN-O7

Epidemiology and clinical audit of gastric carcinoma in a tertiary care hospital

V Sankar , Ratnakar Kini, K Premkumar, Kani Shiek Mohammed, T Pugazhendhi, Mohammed Ali

Madras Medical College, Chennai 600 003, India

Small Intestine

SI-01

Effect of nonabsorbable antibiotic, rifaximin in patients with irritable bowel syndrome: A single centre study

M Ramesh , N Bhagyalekshmi, Xavier Ignatius

M E S Medical College, Perinthalmanna, Malapuram, Kerala 679 338, India

Background: There are many studies addressing the role of rifaximin in irritable bowel syndrome (IBS), however there is no such studies available from India. In this study we are demonstrating the effect of rifaximin, a nonabsorbable antibiotic, in IBS.

Objective: Is to assess the efficacy and safety of short course of rifaximin in IBS patients without constipation.

Methods: This study was carried out in a tertiary care hospital in Kerala. Following simple randamization treatment group received rifaximin 400 mg thrice daily for a period of 2 weeks. Follow up period was one week. Before treatment, after treatment and one week after follow up data was recorded. Subjective feeling of improvement in global IBS symptoms, bloating score, pain score and overall score was used in final analysis. Analysis was done using SPSS version 16.

Result: One hundred and forty-nine patients (75 patients in rifaximin group and 74 control) was included in the study. There was a significant reduction in global IBS symptoms in rifaximin arm when compared to control group (p value <0.001). Assessment at the end of two weeks therapy rifaximin provided significant improvement in the following IBS related symptom scores (bloating score, pain score and overall score). The improvement which was obtained at the end of the treatment was sustained for one week follow up.

Conclusion: A two weeks course of rifaximin in IBS patients provided significant improvement in global IBS symptoms and IBS related scores. No major adverse effect was reported in the study.

SI-02

WITHDRAWN

SI-03

Capsule endoscopy: Role in acute obscure gastrointestinal bleed

Abdul Rauf , A Arora, Pankaj Tyagi, P Sharma, A Kumar, N Bansal, V Singhla

Departments of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, Old Rajender Nagar, Delhi 110 060, India

Introduction: Acute gastrointestinal (GI) bleed is an emergency which require urgent management. There are cases of acute GI bleed in which upper GI endoscopy and colonoscopy did not show bleeding lesion that is acute obscure GI bleed. In such cases the next investigation can be CT angiography, intraoperative endoscopy or capsule endoscopy (CE).

Aim: We investigated the role of CE in acute obscure gastrointestinal bleed (AOGIB) cases.

Method: All patients presenting to our hospital with evidence of AOGIB were included in the study. After normal esophagogastroduodenoscopy (EGD) and ileocolonoscopy CE was performed within 48 hours. The videos were read at a rate of 14 to 20 frames/sec. Abnormalities were recorded.

Results: In the study period of two years out of 230 CE, 25 were done for AOGIB. Nineteen presented with malena and 6 with bright red stools. Six (24 %) patients were on some antiplatelet agents, anticoagulants, or nonsteroidal anti-inflammatory drugs (NSAIDs). CE revealed lesion in 24 out of 25 patients, active bleed was seen in 19 (76 %) patients. Lesion was seen in 13 patients in jejunum and, 11 in ileum. Jejunum showed 6 ulcers, 4 AVM, 2 polyps and one diverticula. Eleven patients had lesion in ileum and all the lesions were ulcers. Out of 25, (64 %) (n=16) improved with conservative management, 4 underwent surgical intervention and five required endoscopic therapy (APC).

Conclusion: CE revealed lesion in 24 out of 25 patients with AOGIB. Most common lesion was ulcers and was most common in ileum. Sixty-four percent improved with conservative management.

SI-04

Celiac disease: Report from central India

Mohd Talha Noor, Manish Tiwari , Bhagwan Singh Thakur

Department of Gastroenterology, Sri Aurobindo Institute of Medical Sciences, Indore 543 111, India

Objective: To study the presentation of celiac disease in a tertiary care hospital of central India.

Material and Methods: Medical records of 17 consecutive patients diagnosed as celiac disease, from January 2012 to December 2013, were analyzed. Evaluation of these patients included detailed history and clinical examination, laboratory parameters like hemogram, liver function tests, blood sugar, stool microscopy, esophagogastroduodenoscopy (EGD) with duodenal biopsy and celiac serology. All patients were followed up for at least 6 month period.

Results: The mean age of presentation was 20.64 (±9.5) year. Mean duration of illness was 4.7 (±2.5) years. Male to female ratio was 1.12:1. Mode of presentation was anemia 76.47 % (13/17), chronic diarrhea 70.58 % (12/17), growth failure 41.17 % (7/17) and flatulence 17.65 % (3/17). Additionally, 2 patients had dysphagia, 3 had chronic liver disease and 1 had vitiligo. IgA TTG test was positive in 15 patients and 2 patients were IgG antigliadin test positive. All patients showed grooving and scallo** of mucosal folds in 2nd part of duodenum (D2) on EGD and 2 patients had an associated upper esophageal web. According to modified Marsh classification 47 % patients had 3A changes, 29.41 % had 3B changes, 23.53 % had 3C changes on D2 biopsy. All patients improved after gluten withdrawal.

Conclusion: Celiac disease is not rare in central India and presents with a variety of clinical manifestations. High index of suspicion is required in patients presenting with symptoms like diarrhea, anemia and growth failure. Timely diagnosis and gluten withdrawal leads to dramatic clinical improvement.

SI-05

Celiac disease: A disease with varied manifestations in adults in India

Vaibhav Somani, Apurva Shah, Deepak Amarapurkar

Bombay Hospital and Medical Research Centre, 12, Marine Lines, Mumbai, 400 020, India

Background : In India incidence of celiac disease is rising and more prevalent in the Northern part of the country, the so-called “celiac belt”, a finding that is at least partially explained by the wheat-rice shift from the North to the South.

Aim and Methods : The aim of the present study was to determine clinical manifestations of celiac disease in western India. In retrospective analysis of prospectively maintained data at single tertiary health centre, patients diagnosed with CD based on modified European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria were evaluated for clinical features, serology and histology of endoscopic duodenal biopsy.

Result: A total 75 patients diagnosed by modified ESPGHAN criteria (46 females, mean age 36±15 years) had positive serology-IgA anti-endomysieal antibody (n-72), IgA anti-tTG antibody (n-3) and 6 %, 28 %, 3 %, 62 % patients had Marsh stage 0, 1, 2, and 3 respectively. Sixty-five percent of patients presented with typical diarrheal disease. One or more associated diseases were noted in 27 (36 %) patients and most common being autoimmune disease (16 %) (hypothyroidism, Grave’s disease, autoimmune hepatitis, DM type 1, rheumatoid arthritis) followed by neurological conditions (9 %) (epilepsy, depression, schizophrenia, ataxia, migraine). Most common atypical manifestations were anemia (76 %) followed by elevated transaminases (39 %), osteopenia (25 %), neurological (4 %) and infertility (1 %).

Conclusion: Celiac disease is also common in western India and atypical manifestations and associated conditions should be actively screened in all CD patients.

Parameters

Number

Percentage (%)

Elevated transaminases

29

38.67

Iron deficiency anemia

57

76

Marsh Staging *

  

 Marsh 0

4

5.63

 Marsh 1

20

28.17

 Marsh 2

2

2.82

 Marsh 3a

1

1.41

 Marsh 3b

16

22.54

 Marsh 3c

28

39.44

IgA anti-endomyceal antibody titres **

  

 < 3 times

30

41.67

 3 to 10 times

31

43.06

 > 10 times

11

15.28

*The total number of patients for Marsh staging was 71 as biopsy report was not available of 4 patients

**The total number of patients whose IgA anti-endomyceal antibody titres was done were 72

SI-06

Appendiceal histology and its clinical significance in ulcerative colitis: A prospective study

Nadeem Pervez , Surinder S Rana, Ritambhra Nada * , Vishal Sharma, Rajesh Gupta ** , Vishal Sharma, Ravi Sharma, Deepak Bhasin

Departments of Gastroenterology, *Histopathology, and **Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: The appendix may be involved in ulcerative colitis and its clinical significance is not clear. We prospectively investigated appendiceal histology and its clinical significance in patients with ulcerative colitis.

Methods: Sixty patients were prospectively enrolled and underwent colonoscopy. The biopsy was taken from appendiceal orifice, cecum and colon. Surgical specimens of the appendix and colon of 9 patients were also analyzed. Appendiceal histology was classified as having active or inactive inflammation or normal.

Results: In patients evaluated endoscopically, 63 % patients had histological involvement of the appendiceal orifice. Appendicular involvement was seen in 55.5 % of patients who underwent surgery. Pancolitis was seen more commonly seen in patients with appendicular orifice inflammation than in patients with normal appendicular histology (44.7 % vs. 9 %, p=0.001). Most patients with appendiceal orifice inflammation had involvement of the cecum. Skip lesion of the appendix without cecum involvement was seen in 37 % of the patients managed medically. Also, 40 % of the patients managed surgically had skip lesions of the appendix. The patients with appendiceal orifice inflammation had a significantly higher grade of endoscopic colitis compared to patients with normal histology (p=.006). Relapse rate were higher in patients with appendiceal orifice inflammation than in patients with normal appendiceal histology (18.4 % vs. 9 %), although insignificant (p=0.329).

Conclusion: Appendicular involvement in ulcerative colitis is not uncommon. Its involvement is more common in patients with pancolitis as well as in patients with higher grade of endoscopic colitis and active appendiceal inflammation may predict higher relapse rates.

SI-07

Ileal histology and its clinical significance in patients with ulcerative colitis

Nadeem Pervez , Surinder S Rana, Ritambhra Nada * , Vishal Sharma, Rajesh Gupta ** , Vishal Sharma, Ravi Sharma, Deepak Bhasin

Departments of Gastroenterology, Histopathology*, and Surgery**, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Little is known about mucosal inflammation in terminal ileum and its clinical consequences in ulcerative colitis. We prospectively investigated the ileal histology and its clinical significance in patients with ulcerative colitis.

Methods: Ileocolonoscopy was performed in 56 patients and biopsy was taken from terminal ileum, cecum and colon. Surgical specimens of the ileum and colon of 9 patients were also analyzed. Patients were followed for a minimum period of 6 months.

Results: In patients evaluated endoscopically, histological inflammation of ileum was seen in 17.8 %. Ileal involvement was seen in 11 % of patients who underwent surgery. Majority of patients had backwash ileitis i.e. along with microscopic involvement of the cecum (90 % in the endoscopy group and 100 % in the surgery group). Pancolitis was seen significantly more in patients with ileal inflammation as compared to patients with normal ileal histology (76 % vs. 26 %, p=0.018). Patients with ileal inflammation had more active disease in colon, although statistically insignificant (p=.136). As regards to relapse rate there was no significant difference between patients with or without ileal inflammation (p=.186).

Conclusion: Ileal involvement in ulcerative colitis is not a common phenomenon. It occurs more often as backwash ileitis and due to more extensive colitis. Ileal involvement does not seem to alter or predict the course of ulcerative colitis.

SI-08

Role of CT enterography in assessing the severity of Crohn’s disease

M K **achandran

Lakeshore Hospital and Research Centre Limited, Kochi 682 304, India

Background/Aims: Crohn’s disease (CD) is a transmural disease. Assessment of inflammation by endoscopy may be incomplete. The present study was done to evaluate the role of CT enterography (CTE) in assessing the severity of Crohn’s disease.

Methods: A retrospective study was done from August 2010 to February 2014. All patients with CD who underwent CTE and ileoscopy within 30 days of the date of CTE were taken into study. CTE was classified as severe if mural hyperenhancement, mesenteric fat density, and engorged vasa recta were all present. Endoscopic severity was assessed by Rutgeerts score (RS), and grouped into 2 group of mild (0-1) and severe (2-5). Patients were grouped into 2 groups of mild (CRP60). A standard group was created by taking cases who had severe disease as shown by 2 out of the 3 modalities. The investigations which independently predicted the standard group were identified by logistic regression.

Results: Sixty-three patients were studied. Mean age: 33±12.5 yrs. M/F:36/27. On CTE, 51/63 had severe disease and 12/63 mild disease. On endoscopy, 30/63 had severe and 33/63 mild CD. CRP and RS, but not CTE, independently predicted the standard group (severe disease) by logistic regression. On ROC analysis, CRP had AUROC of 0.94 and RS had AUROC of 0.79 for severe disease.

Conclusion: CTE was ineffective in predicting the severity of CD when compared to CRP and endoscopy.

SI-09

Infliximab in inflammatory bowel disease: Our 2 year experience at NIMS

R Maidur , B Sukanya, K Chintan, S Sandip, S Nikhil, V Kunal, K P Bubun, Y Raghavendra, N Joshi, Ajit Kumar

Department of Medical Gastroenterology, Nizam’s Institue of Medical Sciences, Punjagutta, Hyderabad 500 082, India

Background: Biologicals have well established role in management of inflammatory bowel disease (IBD).

Aim: To study the effect of infliximab in patients with IBD on standard therapy.

Methods: Fourteen patients of IBD (12 Crohn’s and 2 ulcerative colitis [UC]) receiving infliximab between June 2012 to May 2014 were included and data analyzed retrospectively.

Results: Nine females, 5 males with 85.7 % (12/14) presented in 2nd or 3rd decade. Six had abdominal pain, 4 had diarrhea and 3 had fistulizing disease. Crohn’s involved ileocecum and colon in 5 each and 2 jejunoileal. Stricturizing type (7) was more common than fistulizing type (3) and 2 had both. Infliximab was given within 5 years of diagnosis in 9 and more than 5 years after diagnosis in 4. Three had surgery and 2 took ATT prior to diagnosis. In UC remission was achieved with only induction in both patients however, need for maintenance therapy was noted in 5 patients in CD. Clinical response in the form of reduced stool frequency and pain abdomen was noted in all except one who required reduction in dosing interval presumably due to development of Type II infliximab antibodies. Fistula healed without need for surgery in all patients. Weight gain was noted in 12/14 (85.7 %) of the patients. Improvement in lab parameters was noted in most patients.

Conclusion: Most patients were young females. Fistulizing CD had a good response to infliximab without need for surgery or maintenance therapy. Clinical and laboratory improvement was seen in most patients. Infliximab could avoid colectomy in patients with acute severe UC.

SI-10

Histological features do not predict occurrence of extraintestinal manifestations in celiac disease

Arvind Dambalkar, Vishal Sharma * , Ravi Sharma * , Surinder S Rana * , Ritambhra Nada ** , Pankaj Malhotra, Neelam Verma *** , Sanjay Bhadada **** , Deepak K Bhasin *

Departments of Internal Medicine, Gastroenterology*, Histopathology**, Hematology*** and Endocrinology****, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Celiac disease can have both gastrointestinal and extraintestinal manifestations. There is paucity of data comparing extraintestinal manifestations with histological severity.

Methods: Forty-nine adult patients (mean age: 29.63±10.51 years (32 females) of celiac disease underwent a detailed evaluation including history, clinical examination, hematological, biochemical and serological investigation (IgA TTG titres). These patients underwent upper gastrointestinal endoscopy and esophageal, gastric and duodenal biopsy. Duodenal histology graded as per modified Marsh system. Comparisons vis-a-vis extraintestinal manifestations and duodenal histological severity were made.

Results: Abdominal pain/discomfort was present in 61.2 %, diarrhea in 53.1 %, and 33 % patients had BMI <18.5kg/m2. Amongst extraintestinal features, anemia was present in 65.3 %, hypothyroidism in 16.3 %, infertility/history of miscarriage in 20.4 % and migraine in 14.3 % patients. Elevated AST and ALT levels were seen in 24.5 % and 20.4 % of patients. Marsh 1 changes were seen in 10.2 % patients, Marsh 2 in 12.2 %, Marsh 3B in 46.9 % and Marsh 3C in 30.6 % patients. IgA-TTG levels were significantly more elevated in patients with villous atrophy (Marsh 3B and 3C) as compared to patients without villous atrophy Marsh 1 and Marsh 2). Scallo** and grooving was significantly more commonly observed in patients with Marsh grade 2 and 3C. No differences were observed between various Marsh groups vis-à-vis occurrence of anemia, migraine, reproductive abnormalities, elevated liver enzymes or hypothyroidism.

Conclusions: Extraintestinal manifestations are unrelated to the presence or absence of villous atrophy. Patients with villous atrophy had higher tissue transglutaminase antibody levels but these do not correlate with presence of extraintestinal features.

SI-11

Can narrow band imaging predictduodenal histology in celiac disease? A prospective double blind study

S K Sinha , P K Siddappa, J Basha, K Vaiphei * , K K Prasad, S Appasani, N Berry, M Ashat, K Singh, R Kochhar

Departments of Gastroenterology and Histopathology*, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Celiac disease (CD) is characterized by varying degrees of villous atrophy. Narrow band imaging (NBI) delineates villous patterns better than routine endoscopy.

Aim: To compare diagnostic accuracy of NBI with histopathology in predicting duodenal villous morphology in CD.

Materials and Methods: Study included 116 patients (age 27.2±13.2 years, 67 females), 86 were suspected CD, 14 were follow up patients of CD and 16 had functional dyspepsia. They underwent esophagogastroduodenoscopy (EGD) along with NBI. Images of duodenal mucosa were digitally recorded and subsequently analyzed in blinded manner by two endoscopists. Four duodenal biopsies taken from duodenum were examined by a blinded pathologist. NBI pattern was classified into normal villous pattern (NVP), distorted and blunted villous pattern (DVP) and absent villous pattern (AVP). NBI findings were correlated with histopathology.

Results: EGD showed scallo** in 56.8 % and grooving in 59.4 %. NBI revealed AVP in 46, DVP in 38 and NVP in 32 patients. Among CD (suspected and follow up, n=100) 46 had AVP, 37 had DVP and 17 had NVP on NBI. On histopathology 50 had total villous atrophy, 35 had partial villous atrophy and 15 had no villous atrophy. Four CD patients on gluten-free diet and 12 dyspepsia patients (n=16) had normal villous pattern on both NBI and histopathology. Significant correlation was observed between NBI and histopathology (p<0.001). The overall sensitivity and specificity of NBI for delineating villous pattern were 88.76 % and 81.48 % and the positive and negative predictive values were 94 % and 68.75 % respectively.

Conclusion: NBI can predict villous atrophy with high sensitivity and positive predictive value in CD.

SI-12

Yield of wireless capsule endoscopy at tertiary reference center

Sandeep Nijhawan , Shailendra K Jain, Amritesh Kumar, Amit Mathur, Gaurav Gupta

Department of Gastroenterology, Sawai Man Singh Medical College, J L N Marg, Jaipur 302 004, India

Aim: To study the outcome of capsule endoscopy in patients of obscure gastrointestinal (GI) bleed, pain abdomen.

Method: Data of patient admitted in Gastroenterology Department, from 2012 to 2014 was retrospectively evaluated who underwent capsule endoscopy for obscure GI bleed and other indication.

Result: Total no patients-45, (male-37, female-8). Mean age-54, (SD-18.12). Obscure overt GI bleed-25, obscure occult GI bleed-15, unexplained pain abdomen-4, chronic diarrhea-1. Of 45 patients investigated 41 had some lesion that could explain etiology. Bowel erosion/ulcer due to nonsteroidal anti-inflammatory drugs, Crohn’s, and tuberculosis were commonest (58 %) etiology. Angioectasia were found in 36 % of cases studied. Heavy hookworm infestation was seen in one patient. Mass lesion (GIST) was also seen in one patient. Four patients had negative study (2 patient of pain abdomen, 1 of obscure occult GI bleed, 1 of chronic diarrhea). Of 40 patients of obscure GI bleed 37 patients (92 %) had abnormal finding that could establish the etiology.

Conclusion: This study shows capsule endoscopy could help in diagnosis in patients with obscure gastrointestinal bleed, unexplained pain abdomen, chronic diarrhea. In northern part of India NSAIDs enteropathy and angioectasia were most common cause of obscure GI bleed.

SI-13

Tropical sprue as a possible cause of malabsorption in a young adult

Susant Sethi, Rasmirekha Behera

Apollo Hopitals, Bhubaneshwar 751 013, India

Background: Tropical sprue though had been classically known as a cause of malabsorption is a rare entity today. As etiology is obscure it is largely diagnosed by exclusion of other causes of malabsorption like celiac disease, chronic pancreatitis and parasitic infetions. This recently encountered case did not fit to other causes of malabsorption hence could be a case of tropical sprue.

Case History: A 27-year-old male presented with progressive weight loss (more than 15 kg) for last two years or more, chronic diarrhea (watery some times fatty, non bloody) for 6 months and anorexia with generalized weakness for 3 months. On examination he was found to have aphthous ulcerations and stomatitis in mouth and mild distension of abdomen. Other systemic examination were unremarkable. Blood investigations revealed low serum albumin viamin B12 and D level. ESR mantoux did not support tuberculosis. UGIE revealed scallo** of duodenal mucosal fold and nodularity. H pylori was negative and biopsy revealed mild to moderate villous atrophy, increase in intraepithelial lymphocytes 35-40/20 enterocytes. Serological markers of celiac disease like IgA anti-TTG, EMA and anti-gliadin antibodies were all negative. CECT abdomen revealed diffusely dilated small bowel jejunal loops with segmental thickened enhancing muosa. Colonoscopy revealed mild ulceration and nodularity in terminal ileum biopsy of which was unremarkable. No cryptitis/mild crypt distortion was present. Stool routine and culture was normal. Patient was treated with a course of doxycycline with nutritional support. He started improving and gained 5 kg of weight in on month.

Conclusion: Tropical sprue which is a diagnosis of exclusion needs to looked carefully against other causes of malabsorption. Celiac disease and tropical enteropathy may not be completely differentiated from tropical sprue.

SI-14

Study of prevalence and HLA ty** in first degree relatives of children with celiac disease

Shilpy Singla 1 , Praveen Kumar 1 , Anurag Rohatgi 1 , Gurvinder Kaur 2 , Monisha Choudhury 1 , Lokesh Sharma 1

1Lady Hardinge Medical College and Associated Hospitals, New Delhi, India and 2All India Institute of Medical Sciences, New Delhi 110 029, India

Background and Aim: There is a wide variation in worldwide reported prevalence of celiac disease (2.8 % to 18 %) among first degree relatives of celiac disease patients, with scarce data from India. We conducted this study to evaluate the prevalence of celiac disease among first-degree relatives of children with celiac disease and to study their clinical and genetic profile.

Methods: Sixty-four confirmed celiac disease patients and their 202 first degree relatives (FDRs-parents and siblings) were enrolled. Routine blood investigations and human IgA tissue transglutaminase (IgA tTGA) of FDRs were done after informed consent. HLA DQ 2/8 testing was carried out in 55/64 index cases and 165/202 first degree relatives. All serology positive FDRs were offered endoscopic duodenal biopsy to confirm celiac disease.

Results: Thirty-five (17.3 %) first degree relatives were celiac serology (IgA tTGA) positive, twenty-three consented and underwent endoscopic duodenal biopsy, of which eighteen (8.9 %) showed histology suggestive of celiac disease (Marsh grading IIIa or more). Nine out of thirty-five (22.9 %) IgA tTGA positive FDRs had recurrent loose stools or pain abdomen. Amongst index cases and seropositive first-degree relatives, HLA DQ2 (75.8 %) was found more prevalent than HLA DQ8 (5.2 %); while 11.6 % carried both. One index case and one seropositive first-degree relative had non-HLA DQ2/8 haplotype. The phenotype frequency of HLA DQ2 and DQ8 in first-degree relatives was 79.4 % and 19.3 %, respectively.

Discussion and Conclusions: The present study revealed 17.3 % celiac seropositivity amongst FDRs, while 8.9 % were found to have histology confirmed celiac disease (silent CD), much higher than the general population prevalence i.e. 1 %. Genetic profile of celiac disease patients and their FDRs was found to be different, with HLA DQ8 being more prevalent than reported worldwide (<5 %). Our study highlights the importance of routine screening of all FDRs for celiac disease which is not a practice despite several international recommendations.

SI-15

Structural and functional changes in the tight junctions in asymptomatic and serology negative first degree relatives of patients with celiac disease

Asha Mishra , Shyam Prakash, T K Das, V Sreenivas, Vineet Ahuja, Siddhartha Datta Gupta, Govind K Makharia

Departments of Gastroenterology and Human Nutrition, Pathology, Anatomy and Biostatistics, All India Institute of Medical Sciences, New Delhi 110 029, India

Background: While tight junctions abnormalities are well described in celiac disease (CeD), are the effect or cause of the disease is not well known. In order to demonstrate if tight junction abnormalities are initiating event, we studied structure and function of tight junctions in asymptomatic, anti-tTG Ab negative first-degree relatives (FDRs) of CeD.

Subjects and Methods: Ultrastructure of tight junctions were studied in 12 FDRs and 12 controls, all asymptomatic, anti-tTG Ab negative and having no villous abnormalities. Expression of key tight junction proteins (ZO-1, occludin, claudin-2, 3 and 4 and JAM-A) and zonulin was studied in 24 anti-tTG negative FDRs and 24 controls using qPCR and immunohistochemistry. Functional assessment of tight junctions was done by measuring intestinal permeability (using lactulose mannitol ratio, LMR) in 97 asymptomatic, anti-tTG negative FDRs and 75 healthy controls. Serum zonulin level was also measured in 172 anti-tTG negative FDRs and 198 controls.

Results: Ultrastructural abnormalities such as dilatation of tight junction (p=0.0037) and loss of pentalaminar structure (p=0.001) were more common in FDRs compared to controls. LMR was significantly increased in FDRs as compared to controls [0.48(0.25-0.94) vs. 0.17(0.07-0.53), p=0.05)]. There was significant under-expression of tight junction proteins ZO-1 and occludin in FDRs than controls.

Conclusions: Even asymptomatic, anti-tTG-Ab negative and with normal histology FDRs have both ultrastructural and functional abnormalities in tight junctions. These findings indicate that abnormality in paracellular route is an initial pathogenic event and allows entry of antigen through the tight junctions and may have therapeutic implications.

SI-16

Patients with celiac disease may have normal weight or may even be overweight

Abhishek Agnihotri , Aishwairya Sharma, Anil K Verma, Prasenjit Das, Bhaskar Thakur, V Sreenivas, Vineet Ahuja, Govind K Makharia

Departments of Gastroenterology and Human Nutrition, Pathology, and Biostatistics, All India Institute of Medical Sciences, New Delhi 110 029, India

Background: While patients with celiac disease are expected to have underweight, 8 % to 40 % of them in the West are overweight and some even obese at presentation. We reviewed body mass index (BMI) of our patients with celiac disease and derived correlations between BMI and other disease characteristics.

Patients and Methods: We retrospectively reviewed the case records of 212 paients (>12 years of age) with celiac disease at the Celiac Disease Clinic. Diagnosis of celiac disease was made on the basis of modified ESPGHAN criteria. BMI was classified as per WHO criteria.

Results: Of 212 patients, 117 (55.2 %) were of underweight, 89 (42 %) normal weight, 6 (2.8 %) overweight and none were obese. The proportion of underweights was more in the males as compared females patients with celiac disease (63.2 % vs. 48.7 %, p=0.036). Mean age (95 % CI) of underweight patients was less than that of normal and overweight patients, [22.2 (20.1-24.4) years vs. 33.2 (30.2-36.2) years, p<0.001]. While occurrence of moderate or severe anemia was numerically more common in underweights, (49.6 % vs. 38.3 %), the difference however was not statistically significant (p=0.103). There was no difference in the fold rise in titre of anti-tTG Ab (p=0.166) and severity of villous abnormalities (p=0.231) in underweights compared to rest of the group.

Conclusions: Approximately half of patients with celiac disease patients are of normal weight or even overweight at presentation. Therefore, the diagnosis of celiac disease should be discarded if the subject is of normal weight or even overweight.

SI-17

WITHDRAWN

SI-18

Short-term progression of histology in patients with potential celiac disease

Raghuram Kondala , Ameet Kumar Banka, Alok Sangam, Amarender Singh Puri, Sanjeev Sachdeva

Department of Gastroenterology, G B Pant Hospital, New Delhi 110 002, India

Background: Existing data on natural history of potential celiac disease (PCD) is sparse and limited to a few studies from the West.

Aim: To evaluate short-term histological progression of PCD in Indian patients.

Methods: Patients with PCD were prospectively identified by screening relatives of patients with celiac disease; diarrheal subtype of irritable bowel syndrome; and patients with iron deficiency anemia. IgA anti-tissue transglutaminase antibody was determined by ELISA. Patients with positive serology were subjected to endoscopy with duodenal biopsy. Patients with Marsh-III changes were excluded while rest were retested for serology and histology at 6-monthly intervals for 12 months.

Results: Fifty-seven patients (23 males), mean age 28.7 years (range 4-73 yrs) were diagnosed to have PCD. Duodenal biopsy showed Marsh-0/I/II changes in 28/27/2 patients, respectively. At 6 months, 12 patients became seronegative. The remaining 45 patients continued to be seropositive at 12 months. Histological progression to Marsh-III occurred in only 4 patients while progression from Marsh-0 to Marsh-I or Marsh II occurred in 6 and 1 patients respectively. Fourteen patients with Marsh-I showed regression to Marsh-0. Of the two patients who were initially Marsh II, one remained so at follow up and one showed regression to Marsh 0.

Conclusion: Histological progression to Marsh-III occurred in only 7 % of patients with PCD. These observations do not justify starting gluten-free diet in all patients with PCD.

SI-19

Randomized double-blind placebo-controlled trial of antibiotic treatment in patients with irritable bowel syndrome directed against small intestinal bacterial overgrowth diagnosed using jejunal aspirate culture

Uday C Ghoshal , Deepakshi Srivastava, Ujjala Ghoshal * , Asha Misra

Departments of Gastroenterology and *Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014, India

Objective: Antibiotics relieve symptoms in half of un-selected patients with irritable bowel syndrome (IBS), but their efficacy when selected according to small intestinal bacterial overgrowth (SIBO) tests is unknown.

Method: Eighty IBS-patients (Rome-III) were randomized (computer generated stratified) to 10-days norfloxacin or placebo based on presence (>105 CFU/mL on upper gut aspirate culture) or absence of SIBO. Symptom-score, Rome-III criteria, aspirate-culture and glucose hydrogen breath test (GHBT) were studied before, one-month post-treatment and then followed up till 6-months.

Results: Of 15 (19 %) with SIBO on culture (4 on GHBT too), 8 received norfloxacin and 7 placebo; of other 65, 32 norfloxacin and 33 placebo. More patients with SIBO (>105 CFU/mL) turned Rome-III negative with norfloxacin at one month than those without colonization (<103 CFU/mL) (7/8 [87.5 %] vs. 3/21 [14.3 %], p=0.0005) and there was a trend among moderately colonized (>103 to <105 CFU/mL) (5/11 [45.5 %] vs. 3/21 [14.3 %], p=0.08) but none with placebo. Norfloxacin improved symptom-score (SIBO:6.5 [2-13] vs. 2 [0-10], p=0.01; moderate colonization:10 [2-16] vs. 5 [1-12], p=0.005; non-colonized:8 [3-16] vs. 5 [0-12], p<0.001) not placebo (10 [5-13] vs. 11 [2-14], p=ns; 6 [4-12] vs. 6 [4-12], p=ns; 9 [1-17] vs. 9 [2-18], p=ns, respectively) at one-month. At 6-months, symptom-scores among norfloxacin group were: SIBO: (3 [1-10]); moderate colonization: (6 [0-12]); non-colonized: (7 [1-11]); Rome-III criteria remained negative in 2/8 (25 %), 3/11 (27.5 %) and 2/21 (9.5 %), respectively. All 4/8 consenting patients with norfloxacin became SIBO-negative (2 by culture and GHBT and 2 by GHBT alone) but none of 7 with placebo.

Conclusion: Norfloxacin was more effective than placebo in relieving symptoms of SIBO-associated IBS.

Large Intestine

LI-01

Clostridium difficile infection in a tertiary care hospital of North India

Chetana Vaishnavi , Meenakshi Singh, Prashant Kapoor, Rakesh Kochhar

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Clostridium difficile is the primary cause of hospital acquired colitis in patients receiving antibiotics and is involved in the exacerbation of inflammatory bowel disease (IBD). Pathogenicity of C. difficile is due to production of toxin A and B. The clinical and demographic profile of inpatients and outpatients reporting for C. difficile infection to a tertiary care hospital was analyzed. Laboratory records of clinical and demographic data recorded in a pre-printed proforma were reviewed. Stool samples from a total of 3,044 patients processed for detection of C. difficile toxins (CDT) A and B by enzyme linked immunosorbent assay were included. Of the 3,044 cases of all age groups, 62.5 % were males and 7.8 % patients had IBD. The major antibiotic groups in use were nitroimidazole, penicillin, quinolones including fluoroquinolones, glycopeptides and carbapenems. Predominant symptoms present were diarrhea (90.2 %), abdominal pain (36.5 %) and fever (40.6 %). C. difficile toxins were positive in 17.5 % of the patients. Among IBD patients 19 % were positive for CDT. There was no significant association with age group or gender for CDT positivity. CDT positivity was highly associated with gastrointestinal diseases (21.1 %), renal diseases (20.8 %), surgical conditions (20.7 %) hepatic disorders (18.5 %) and cancers (17.6 %). In CDT positive cases fever was present in 41 % and abdominal pain in 37.9 %. C. difficile infection is prevalent among patients in our hospital, particularly in those with gastrointestinal diseases. Clinical features of the patients correlating with toxin detection can be a valuable asset for laboratory diagnosis of the disease.

LI-02

Association of SNP rs11614913 with ulcerative colitis in North Indian population and its effect on the expression profile of miR-196a-2.

Raju Ranjha 1 , Vineet Ahuja 2 , Jaishree Paul 1

1School of Life Sciences, Jawharlal Nehru University, New Delhi, India, 2Department of Gastroentrology, All India Institute of Medical Sciences, New Delhi 110 029, India

MicroRNA are small ribonucleic acid molecules that alters the expression of its target gene by binding to 3`UTR of target mRNA. SNP rs11614913 in miR-196a-2 is found to have association with the risk and prognosis of multiple-types of inflammatory diseases and tumors. Our aim of this study was to find out the association of SNP rs11614913 with inflammatory bowel disease in north Indian population and effect of polymorphism on the expression profile of miRNA. Genomic DNA was extracted from blood specimen and total RNA was extracted from biopsy sample. miR-196a-2 polymorphism was genotyped using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and expression analysis was done using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). TT genotype of miR-196a-2 was associated with decreased risk of UC compared to CC genotype, p=0.031, OR=0.497 (0.264- 0.935). Expression of miR-196a-2 was dependent on the genotype of patients and controls. Genotype changes at the level of SNP in miR-196a-2 gene affect the susceptibility of individual toward ulcerative colitis and also affect the expression of mature miR-196a-2. So the expression of its target genes may be affected due to this which may be of further importance in the study of disease development and its pathophysiology.

LI-03

Haplotype analyses of DNA repair gene polymorphisms and their role in ulcerative colitis

Avinash Bardia , Santosh K Tiwari, Sivaram Gunisetty, Sandeep K Vishwakarma, Pratibha Nallari, Aleem A Khan, Md. Aejaz Habeeb

Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500 058, India

Background and Aim: Ulcerative colitis (UC) is a major clinical form of inflammatory bowel disease (IBD). Genetic variations in DNA repair may impact repair functions, DNA damage, and UC. Hence the work reported in the present paper was designed with an objective to investigate the role of genetic polymorphisms of the genes involved in DNA repair mechanisms.

Methods: A total of 171 patient and 213 controls were included. Genoty** was carried out by ARMS PCR and PCR-RFLP method. Allelic and genotypic frequencies were computed in both control and patient groups and appropriate statistical tests were employed.

Results: The frequency of 'A' allele of hMSH2 was found to be predominant in UC group compared to controls with a 1.64 folds increased risk for UC (OR 1.64, 95 % CI 1.16-2.31, p=0.004). CT genotype of XRCC3 gene was found to be predominant in the UC group compared to controls with 1.75 folds increased risk for UC, which was statistically significant (OR 1.75, 95 % CI 1.15-2.67, p=0.03). GC genotypic frequency of RAD51 was found to be predominant in UC group (50.3 %) compared to controls (38 %) with the difference being statistically significant (p= 0.02). In the control group, the SNP loci combination of hMSH2: XRCC3 were in perfect LD. The GTC and ACC haplotype was found to be predominant in UC than controls with a 2.28 and 2.93 fold significant increase risk of UC.

Conclusion: Polymorphisms in XRCC3, RAD51 and hMSH2 significantly increased the risk of UC in our population.

LI-04

Influence of genetic polymorphisms in X-ray repair cross-complementing group-1 and apurinic/apyrimidinic endonuclease-1 on apoptosis and ulcerative colitis

Avinash Bardia 1, Santosh K Tiwari 1 , Sivaram Gunisetty 1 , Sandeep K Vishwakarma 1 , Pratibha Nallari 1 , Aleem A Khan 1 , Md. Aejaz Habeeb 1*

1Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500 058, India, 2Department of Genetics, Osmania University, Hyderabad 500 007, India

Background: Ulcerative colitis is one of the two major manifestations of inflammatory bowel disease. Base excision repair (BER) is an important DNA repair mechanism which every cell utilizes to repair the damaged DNA. X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) are two vital DNA repair proteins that play definitive roles in BER pathway. Genetic polymorphisms in these genes have been reported to increase the susceptibility of various cancers; however their precise role in apoptosis and etiology of ulcerative colitis still remains elusive. Therefore the present study was designed to examine the polymorphisms in XRCC1 and APE1 and their role on the rate of apoptosis and ulcerative colitis risk.

Methods: Blood samples from 384 unrelated subjects (171- UC, 213-healthy controls) were collected. Genomic DNA was isolated and genotyped for XRCC1 Arg399Gln and APE1 Glu148Asp. Apoptosis and intracellular ROS levels in peripheral blood mononuclear cells were measured using annexin-V and H2DCFDA assay respectively.

Results: The frequency of genotype Arg/Gln at codon 399 of XRCC1 and APE1 Asp/Glu at 148 codon gene was statistically significantly in patients with UC than the controls. High rate of apoptosis coupled with elevated ROS levels were seen in UC subjects than the controls (p=0.01). Increased percentage of necrotic and late apoptotic cells were observed among UC subjects with XRCC1 Arg399Gln and those with both XRCC1 Arg399Gln and APE1 Asp148Glu.

Conclusion: Polymorphisms in XRCC1 Arg399Gln and APE1 Asp148Glu significantly increased the apoptotic rates and risk of ulcerative colitis in our population.

LI-05

WITHDRAWN

LI-06

Clinical activity assessment in ulcerative colitis does not correlate with endoscopic activity always

Mohamed Shihab , Varghese Thomas

Department of Gastroenterology, Government Medical College, Calicut 673 008, India

Background: It is generally assumed that disease activity of ulcerative colitis (UC) is related to the mucosal disease activity.

Aim: To determine whether there is any strong correlation between clinical and endoscopic assessment of disease activity in UC.

Method: Patients with biopsy confirmed UC with active disease or remission were studied. Clinical activity was assessed by Truelove and Witts scoring and endoscopic assessment was done as per Schroeder endoscopic score.

Results: One hundred patients with ulcerative colitis including 36 in remission were studied. Sixty-five percent (n=65) had left sided colitis, 24 % (n=24) had proctitis and 11 % (n=11) had extensive colitis. In the group with active disease, 30 % (n=30), 21 % (n= 21) and 14 % (n=14) had mild, moderate and severe disease respectively. On endoscopic assessment, 48 % (n=48), 24 % (n=24) and 20 % (n=20) had mild, moderate and severe disease respectively. In 30 patients with mild disease clinically, 64 % had mild disease endoscopically. Out of 14 patients with severe disease, 71 % had severe disease endoscopically. In patients with moderate clinical disease (n=21), 43 % had moderate and 34 % severe activity respectively. Patients with isolated proctitis had more endoscopic severity (11 %) and less clinical severity (0 %). Correlation between clinical and endoscopic activity is 0.693 (moderate positive correlation). Measure of agreement in between clinical and endoscopic remission is less (0.391).

Conclusion: There is positive correlation between clinical activity assessment and endoscopic activity in only 70 % of patients with either mild or severe UC. Measure of agreement between clinical and endoscopic activity for moderate disease, isolated proctitis and remission was poor.

LI-O7

Etiological spectrum of lower gastrointestinal endoscopy at a tertiary care centre

Eswar Moparty , P Shravan Kumar, M Umadevi, M Ramanna

Department of Gastroenterology, Gandhi Medical College, Padmarao Nagar, Secunderabad 500 020, India

Aim of the Study: To evaluate the spectrum of clinical etiologies of lower gastrointestinal (GI) endoscopy at a tertiary centre.

Materials and Methods: This retrospective study was conducted at Department of Gastroenterology for a period of 6 months. All the patients subjected to lower GI endoscopy from January to June 2014 were included, irrespective of the indication for which the investigation was conducted. Both sigmoidoscopy and colonoscopy were included, and histopathological evaluation was done when necessary

Results: Total 165 procedures performed; 51 (30.9 %) sigmoidoscopies and 114 (69.09) were colonoscopies. Age range was from 5-78 years; male 96 (58.18 %) and female 69 (41.81 %).

Sl. Number

Findings

Number of cases

Percentage (%)

1

Normal

69

41.81 %

2

Hemorrhoids

29

17.57 %

3

Malignancies

17

10.3 %

4

IBD

15

9.08 %

 

UC

12

7.27 %

 

Crohn’s

3

1.81 %

5

Colostomy/ileostomy

10

6.06 %

6

Proctitis

 (including radiation proctitis)

7

4.24 %

7

TB/Koch's

7

4.24 %

8

Polyps

4

2.42 %

9

Anal fissures

2

1.53 %

10

Nonspecific colitis

2

1.53 %

11

Telengectasia

1

0.6 %

12

Portal HTN colopathy

1

0.6 %

13

Diverticulae

1

0.6 %

Conclusion: Pathological findings found in 96 patients (58.19 %); 69 patients (41.81 %) had normal study. Hemorrhoids was most common pathology.

LI-08

A prospective randomized controlled trial to evaluate the efficacy of placebo versus amitryptiline versus loperamide versus gut directed hypnotherapy in the treatment of irritable bowel syndrome with diarrhea

Sandeep Kunhikannan , Varghese Thomas

Department of Gastroenterology, Government Medical College, Calicut 673 008, India

Background and Objectives: Irritable bowel syndrome (IBS) is a chronic disorder without any definite cure. Many treatment options are available which are not satisfactory. We studied the efficacy of placebo, amitryptiline, loperamide and gut directed hypnotherapy in irritable bowel syndrome with diarrhea (IBS-D).

Methods: Seventy-three consecutive patients with IBS-D (Rome III) criteria were studied. They received therapy for 6 weeks with either placebo (Group A), amitryptiline 10 mg (B), loperamide 2 mg (C) or GHT (D). Reassessment of pain, bowel frequency, general well being, toilet time per week and quality of life were done at 3 weeks, 6 weeks and 3 months.

Results: The baseline characteristics were similar in all groups. Regarding abdominal pain and general well being, short-term benefit was observed in all groups except A, while long-term benefit was observed only in group D. Average stool frequency was found to be significantly reduced in hypnotherapy group (p=0.003). Compared to placebo, total toilet time spent for defecation was found to be reduced in all groups. At 6 weeks, the change in QOL was statistically significant in group B and C as against placebo; but this effect was not seen at 3 months. Long-term efficacy and sustained improvement in QOL was observed only in Group D at 3 months (p=0.004).

Conclusion: Gut directed hypnotherapy (GHT) is more effective than medical therapy in providing short-term and long-term benefits in IBS-D patients. Both loperamide and amitryptiline provided significant relief of symptoms initially and there were no statistically significant difference in the benefits obtained between these drugs.

LI-09

Clinical, endoscopic and histopathological parameters at presentation that predict need for long-term immunosuppression in ulcerative colitis

Ranjit K Sreerama, Puneet Chhabra , Vishal Sharma, Ritambhra Nada * , Ravi Sharma, Chalapathi Rao, Rajesh Gupta ** , Lileswar Kaman ** , Surinder S Rana, Deepak K Bhasin

Departments of Gastroenterology, *Histopathology and **Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Clinical course of ulcerative colitis (UC) ranges from a mild course with prolonged periods of remission to severe disease requiring long-term immunosuppression for disease control. There is limited data on the predictors of need for immunosuppression at presentation.

Objective: To evaluate clinical, endoscopic and histopathological parameters at presentation in patients with UC that predict the need for long-term immunosuppressive therapy.

Methods: We studied 81 patients (males; 40; mean age 38.69±12.90 years) with UC (41 prospectively and 40 retrospectively). The clinical presentation, duration, extraintestinal features, extent of disease, hematological and biochemical features, histology and outcome (drugs, surgery, and mortality) were recorded and analyzed. Subgroup analysis was done after dividing the patients into two groups depending upon whether they needed long-term immunosuppressants or not.

Results: The presenting symptoms were bloody stools (100 %), mucus in stools (98.8 %), abdominal pain (35.8 %), anorectal pain (14.8 %) and extraintestinal symptoms (4.9 %). Of these 81 patients, 7 (8.6 %) patients required surgery and two (2.4 %) patients died. Long-term immunosuppressants were used in 19 patients (azathioprine 16, mycophenolate mofetil 2 and Tacrolimus 1). The patients who received immunosuppressants had higher prevalence of pancolitis (47.4 % vs. 16.1 %, p=0.005). Other clinical, hematological and histological parameters like inflammatory grade, chronicity grade, cellular infiltrates, submucosal fibrosis, Paneth cell metaplasia, and presence of neuronal cells were similar in the two groups.

Conclusion: Of the clinical, biochemical, endoscopic and histological features at presentation only the presence of pancolitis predicts need for long-term immunosuppressants in ulcerative colitis.

LI-10

Allelic polymorphism in IL-6 and IL-10 cytokine genes in ulcerative colitis

Manish Kumar Tripathi , A Ranjan, J K Choudhary, N Gupta, N Singh, V K Dixit, S K Shukla, A K Jain

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India

Background: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) and is often confused with irritable bowel syndrome (IBS). Ulcerative colitis is treated as an autoimmune disease. It has been reported that inflammatory cytokines play important role in the development of the disease.

Aim: To evaluate the role of cytokines IL-6 and IL-10 gene polymorphism in UC and IBS patients.

Method and Materials: In this study we enrolled 56 patients of IBS, 36 patients of UC and 16 healthy controls (HC). Blood samples were obtained after informed consent for DNA isolation. PCR for IL 10 (-1082, -819, -592) followed by restriction digestion using enzyme Mnl1, RsaI and MaeIII was done. For IL-6 PCR was done using double set of primers. The products obtained were analyzed on 2 % agarose gel.

Results: In case of IL-10-1082 both IBS and UC patients and HC showed dominance of AA genotype having 57.1 %, 61.1 % and 62 %. For IL-10-819 maximum number of IBS patients i.e. 39 % and 50 % of healthy controls showed CC genotype whereas 57 % of UC patients had CT genotype. In case of IL-10-592 majority of IBS i.e. 64.3 % and 44 % of UC patients showed AA genotype. IL-6 was found that equal number of UC and IBS patients i.e. 67 % and 75 % of HC were high producer GG genotype.

Conclusion: Results indicate low production of anti-inflammatory cytokines IL-10 in patients with UC and IBS. For IL-6 we found that the IBS and UC patients showed almost equal genotypic distribution.

LI-11

Is clinically silent idiopathic ulcerative colitis always histologically silent?

Ritambhra Nada * , N Pervez, S S Rana, R Gupta, K Singh, D Dhaiya ** , D K Bhasin

Departments of Histopathology*, Surgery** and Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Aims: To correlate histological severity of idiopathic ulcerative colitis (IUC) with clinical remission and relapse.

Methods: Colonic biopsies of 60 consecutive patients of IUC were analyzed and graded for histological activity and chronicity. Histologic findings were correlated with clinical and endoscopic findings.

Results: Out of 60 patients evaluated, most of them were in remission clinically (90 %), whereas only one third of them had inactive histology; two third had histologically active (mild-moderate) disease. Endoscopically also only 12 % were in remission whereas mild, moderate and severe colitis was present in 58 %, 17 %, 13 % respectively. These differences were statistically significant. Mild to moderate active changes were present in quarter each of biopsies. Severe colitis was also documented in 15 % biopsies which was significantly more than endoscopically severe disease in clinically silent or mild-moderate disease. Chronic changes were present in most biopsies ranging from severe (58.7 %), moderate (29.6 %) and mild (11.7 %). Relapse was seen in 8 patients all of whom had moderate to severe chronic changes and some degree of activity (Grade 1, 2 and 3 in 3, 2 and 3 cases respectively).

Conclusion: Smoldering, mild-moderate active inflammation in background of chronicity is virtually present all silent cases of IUC in remission. Patients with higher degree of both chronic and active changes experienced relapse.

LI-12

A comparative parallel prospective open labelled randomized study to assess the efficacy of rifaximin vs vsl#3 versus relaxation therapy in patients with IBS-D

Pravir Gambhire , Ashok Mohite, Samit Jain, Vinay Zanwar, Ajay Choksey, Pravin Rathi

Department of Gastroenterology, B Y L Nair Charitable Hospital and T N Medical College, Mumbai Central, Mumbai 400 008, India

Background: Irritable bowel syndrome (IBS) is a chronic condition. Clinically important benefits might be achieved in patients with preprobiotics and rifaximin in IBS-D owing to altered microbiota, similarly relaxation therapy has been tried owing to altered Brain Gut Axis.

Aims and Objective: Assess the efficacy of rifaximin vs. VSl#3 vs. relaxation therapy for patients with IBS-D in terms of IBS severity score, SGA and QOL during treatment for 15 days and periodic follow up till 6 months.

Materials and Methods: It was a comparative parallel prospective open labelled randomized study. Male/female patients between 18 to 65 yrs, IBS-D as per Rome III criteria, were included, patients were randomized to 3 groups, Group A (rifaximin) 400 mg TID for 14 days, Group B (VSL#3) bid for 14 days and Group 3 (supervised relaxation therapy) for 14 days. Therafter the patients were followed up monthly for 6 months and were assessed for IBS severity score, SGA and QOL at each visit.

Results: (1) Till 3 months, IBS severity score, SGA Score and QOL improved in rifaximin group f/b VSL#3 group f/b relaxation therapy group (p<0.005), (2). Relaxation therapy took 3 to 4 month to act, (3). At the end of 6 months IBS severity score, SGA score and QOL improved in relaxation therapy group f/b rifaximin group f/b VSL#3 therapy group (p<0.005).

Conclusions: (1). For short-term relief of symptoms rifaximin was better, (2). At the end of 6 months relaxation therapy stood better than rest therapies.

LI-13

Efficacy of argon plasma coagulation compared with topical formalin application for chronic radiation proctopathy

S Kavitha, Vadivel Kumaran, Kani Sheik, Rathnakar Kini, K Premkumar, T Pugazhendhi, Mohammed Ali

Department of Medical Gastroenterology, Rajiv Gandhi Government General Hospital, Park Town, Chennai 600 003, India

Background: Chronic radiation proctopathy is a troublesome complication of radiotherapy. Currently the application of formalin therapy (AFR) to the rectal mucosa and the thermal ablation with argon plasma coagulation (APC) are the most promising options.

Aim: To compare the efficacy and safety of formalin therapy to the rectal mucosa and the thermal ablation with argon plasma coagulation.

Materials and Methods: Study was done between June 2013 to May 2014. Fourteen patients with chronic radiation proctitis were treated. Seven patients were treated with instillation of 50 mL 4 % formalin into the rectum. The total mucosal contact time was approximately 20 minutes. Seven patients were treated with APC. Their tolerance to treatment, clinical response, complications and number of sessions were assessed. Patients were considered to be responders if there is was no further bleed or 10 % increase in hemoglobin from baseline.

Results: Hemoglobin level before therapy was 7.4 gms. Patients received an average of 1.7 sessions for APC and 1.5 sessions for AFR. In the APC group, 3 of 7 responders required only a single session, while in the AFR group, 4 of 7 patients responded after a single session. In APC group, the mean hemoglobin level increase was 10 g/L at three months follow up, compared with 10.4 g/L in the AFR group

Conclusions: This study suggests that AFR is more effective and safe than APC to control hematochezia caused by chronic radiation proctopathy. Further studies are needed to confirm this observation.

LI-14

A study on cytokine response in diarrhea predominant irritable bowel syndrome

M Tarakeshwari , K Muthukumaran, G Ramkumar, R Balamurali, T Rajkumar Solomon, P Ganesh

Department of Digestive and Health Diseases, Kilpauk Medical College, Anna Nagar, Chennai 600 010, India

Aim: To estimate serum levels of proinflammatory cytokine TNF-α in adult patients of diarrheal type of irritable bowel syndrome.

Materials and Methods: A Prospective case control study was carried out among diarrhea predominant irritable bowel syndrome (IBS) patients attending our institute. Patients aged 18-75 years with diarrhea predominant IBS fulfilling ROME III criteria were included in the study. Age and sex matched healthy volunteers were taken as control group. Pregnant women, immunodefecient patients, those diagnosed with lactose intolerance and psychiatric patients were excluded from the study. Both the A total of 38 patients were included in case group and an equal number of age and sex matched population were taken as study group.There was a significant difference (p<0.05) in serum levels of TNF α between IBS–D patients (15.9±2.2 pg/mL) and healthy controls (6.92±2.5 pg/mL). There was a significant correlation between TNF α levels and abdominal pain (p=0.03). There was no correlation between abdominal bloat, stool frequency with serum legroup of patients were subjected to clinical examination and investigated for thyroid dysfunction, acute inflammatory markers. Sigmoidoscopy and biopsy was done to rule out microscopic colitis. Cytokine assay was done from peripheral blood sample by ELISA.

Results: A total of 38 patients were included in case group and an equal number of age and sex matched population were taken as study group. There was a significant difference (p<0.05) in serum levels of TNF α between IBS–D patients (15.9±2.2 pg/mL) and healthy controls (6.92±2.5 pg/mL). There was a significant correlation between TNF α levels and abdominal pain (p=0.03). There was no correlation between abdominal bloat, stool frequency with serum levels of TNF α.

Conclusion: Increased levels of proinflammatory cytokine is seen in patients with IBS–D suggesting an underlying inflammation. There is a significant correlation between abdominal pain and TNF α levels.

LI-15

Temporal change in phenotypic behavior in patients with Crohn’s disease

Rishikesh Kalaria , Devendra Desai, Philip Abraham, Anand Joshi, Tarun Gupta, Sudeep Shah

Division of Gastroenterology, P D Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai 400 016, India

Introduction: Studies from the west suggest that one-third patients have aggressive disease behavior at presentation and half of all patients will progress to complicated disease behavior in 20 years.

Aim: To assess the disease behavior in Crohn’s disease at diagnosis, 5 and 10 years using Montreal classification.

Methods: Data of patients with Crohn’s disease were taken from inflammatory bowel disease database. Their baseline details were recorded and Montreal class was entered.

Results: One hundred and seventy-eight patients (median age 35 years, men:97) were included for analysis.

Disease Behavior

B0

B1 N (%)

B2 N (%)

B3 N (%)

Baseline (n=178)

 

133 (74.71)

38 (21.34)

7 (4.49)

5 yrs (n=105) (p=0.178582)

At presentation

0

77 (73.33 %)

24 (22.85)

4 (3.8)

5 yrs

3 (2.85)

74 (70.47)

18 (17.14)

10 (9.52)

10 yr (n=38) (p=0.6483)

At presentation

 

28 (73.68 %)

11 (28.9)

2 (5.2)

5 yrs

1 (2.63)

25 (65.78)

8 (21.05)

4 (10.52)

10 yrs

1 (2.63)

24 (63.15)

9 (23.68)

4 (10.52)

15 yrs (n=18) (p=0.784506)

At presentation

 

12 (66.66)

6 (33.33)

 

5 yrs

1 (5.55)

12 (66.66)

4 (22.22)

1 (5.55)

10 yrs

 

12 (66.66)

5 (27.77)

1 (5.55)

15 yrs

2 (11.11)

11 (61.11)

3 (16.66)

2 (11.11)

Eighty-six patients were given azathioprine and 21 (11 %) TNF α inhibitors. Surgical intervention was done in 12 for B2, 11 for B3 and 1 diagnostic for B2 (Repeat surgeries- 4 patients).

Perianal disease was seen in 21 (11 %) patients at diagnosis (surgery in 10 in 5 years; 3 given TNF inhibitors. At 5 years, 9 new patients developed perianal complications.

Conclusions: In CD patients, at presentations a fourth of patients had aggressive disease. After 5, 10 or 15 year follow up, behavior was statistically not different.

LI-16

Randomized controlled trial comparing the efficacy of measalamine and oral steroids in patients with moderately active ulcerative colitis

Amit Raj , Jayanta Samanta, Yalaka Rami Reddy, Saroj Kant Sinha, Chetana Vaishnavi, Kamal K Prasad, Manik Lal Thakur, Pradeep Kumar Siddappa, Kartar Singh, Rakesh Kochhar

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Aims: To compare the efficacy of oral mesalamine with that of oral prednisolone in patients with moderately active ulcerative colitis (UC).

Methods: Consecutive patients of moderate UC were randomly assigned to two groups :mesalamine 800 mg, 2xTID (ASA) and prednisolone (CS) in tapering doses starting 40 mg/day. Mayo score, sigmoidoscopy with biopsy, and fecal calprotectin (FC) were determined at baseline and at 6 weeks.

Results: Mucosal healing was achieved in 19/29 (65.5 %) in ASA group and 17/25 (68 %) in CS group (p=0.847). There was significant improvement in Mayo score from 8.5±1.2 to 3.5±1.7 in ASA and from 8.1±1.6 to 3.1±1.8 in CS group (p=0.001). Clinical response was achieved in 26 (89.7 %) in ASA group and 23 (92 %) patients in the CS group (p>0.05) and clinical remission in 8 (27.6 %) and 12 (48 %) patients respectively (p>0.05). Total histopathology score in CS group decreased from 11.9±2.4 to 8.1±3 (p=0.001), but ‘end of treatment' total score in both ASA and CS groups were not significantly different, p=0.088). There was improvement in FC levels (132±136.6 μg/g to 75.9±77.1 μg/g in ASA group and in CS group (165.7±116.4 μg/g to 115.6±83.1 μg/g) paired samples did not reach significance (p=0.057 and p=0.136 respectively). In subgroup analysis, there was improvement in FC levels (p=0.007) at 6 weeks in patients who achieved mucosal healing as compared to those who did not (p=0.783).

Conclusion: Prednisolone and mesalamine are equally effective in inducing mucosal healing and clinical response in moderately severe UC. Mucosal healing was positively correlated with fall in FC levels.

LI-17

Distribution of colorectal cancer undergoing colonoscopy

N Sudhan , N Muthukumaran, G Ramkumar, R Balamurali, T Rajkumar Solomon, P Ganesh

Department of Digestive Health and Diseases, Kilpauk Medical College, Chennai 600 010, India

Aim: To study the distribution of colorectal malignancy with respect to age, sex and location of tumor within the colon.

Materials and Methods: Retrospective study from 2009 to 2014. All patients with histologically proven malignancy were included in the study.

Results: Out of 266 patients with colorectal cancer 138 (51.9 %) were males and 128 (48.1 %) were females with the mean age of 58 years in males and 53 years in females. Mean age for colonic carcinoma was 56 years with male:female ratio of 1.5:1. Mean age for rectal carcinoma was 55 years with male:female ratio of 1:1.3. In patients less than 40 years, colonic carcinoma is seen in 12 patients (out of 138 colonic carcinoma i.e. 8.7 %) with male:female ratio of 1:1.4 and rectal carcinoma was seen in 21 patients (out of 128 rectal malignancies i.e. 16.4 %) with male:female ratio of 1:4. Only 19.2 % of cases occurred above 65 years of age. Among distribution of colorectal cancers within colon 48 % were rectal carcinoma and 25 % were ascending colon carcinoma predominantly.

Conclusion: Thus colorectal cancer in our region occurred almost more than a decade earlier than the western population. About two-third of cases in this series occurred between 40 to 65 years of age. There is significant female predominance compared to males in the occurrence of colorectal carcinoma in patients less than 40 years of age.

LI-18

Fecal calprotectin and its correlation with C-reactive protein and ESR in Indian patients with inflammatory bowel disease

Hrishikesh Samant , Devendra Desai, Philip Abraham, Anand Joshi, Tarun Gupta, Alpa Dherai

P D Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400 016, India

Introduction: There is little data on fecal calprotectin levels (FC), a non-invasive marker of disease activity,1 in Indian patients with inflammatory bowel disease (IBD).

Objective: To study FC levels in patients with IBD and its correlation with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

Methods: Records of IBD patients who were tested for FC, CRP, ESR and colonoscopy between 2012 and 2014 were retrieved. Sixty-four patients (44 IBD [24 ulcerative colitis {UC}, 20 Crohn’s disease {CD}) and 20 patients with irritable bowel syndrome (IBS; normal colonoscopy and histology) were included.

Results: The median values of FC, CRP, ESR in patients with IBD and IBS are as below:

 

UC

CD

IBS

p 1

p 2

FC (□g/g)

1800

486.5

67

0.001

0.001

CRP (mg/L)

18

12

6

0.02

0.06

ESR (mm in 1st h)

29.5

29

20

0.5

0.14

p 1: p value between UC and IBS. p 2: p value between CD and IBS

The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of FC, CRP and ESR in endoscopically active IBD are as below:

 

Endoscopically active disease (n=44)

Sensitivity

Specificity

PPV

NPV

FC >200 □g/g

37

84

80

90

70

CRP+ve

29

65

70

90

30

ESR >20 mm in 1st h

28

63

69

87

36

There was no correlation between FC levels and CRP (Spearman’s r=0.19, p=0.2) and between FC levels and ESR (r=0.18, p=0.22).

Conclusion: Patients with UC had higher median concentration of FC than those with CD. FC was better than ESR and CRP in detecting inflammation and does not correlate with either.

Reference: 1. Lin JF, Chen JM, Zuo JH, et al. Fecal calprotectin for assessment of IBD activity: a meta-analysis. Inflamm Bowel Dis. 2014; 20:1407-15.

LI-19

Solitary rectal ulcer syndrome: The clinical, endoscopic and histological series of 92 patients from a tertiary care hospital in North India

M K Behera , V B Abhilash, S Budhiraja, P Asati, V K Dixit, A K Jain

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University,Varanasi 221 005, India

Background: Solitary rectal ulcer syndrome (SRUS) is a chronic, benign defecation disorder often related to excessive straining. SRUS is diagnosed based on clinical symptoms, endoscopic and histological findings.

Methods: All the patients diagnosed with SRUS by colonoscopy and confirmed by histopathology from August 2010 to February 2014 in the Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, India were included in the study. The medical records were reviewed retrospectively to evaluate the clinical, endoscopic and histological findings of these patients.

Results: A total of 92 patients were reviewed retrospectively. Mean age of the group was 41±19 years with age range of 10-82 years; males were 58 (63 %) with male to female ratio of 1.7::1. Bleeding per rectum was present in 83 %, constipation in 46.7 %, abdominal pain in 27.2 %, and diarrhea in 25 % of the patients. Endoscopically, ulcerative lesions in 83 % patients of whom solitary and multiple lesions were present in 44 % and 39 % respectively. Polypoidal lesions were reported in 17.4 % while rectal polyps and erythematous mucosa were found in 5.4 % and 2.2 % respectively. Histological examination revealed fibromuscular obliteration in 100 % of patients, surface ulceration in 70.6 % and crypt distortion in 20.65 % of patients.

Conclusion: Rectal bleeding was the most common symptom and ulcerative lesions were the common endoscopic finding. The non-specificity of the clinical and endoscopic features of SRUS can be confused with the other diseases of rectum, so the histopathology remains the cornerstone for the diagnosis of SRUS.

LI-20

Anti-tissue transglutaminase antibody staining of intestinal biopsies is not specific for celiac disease but is a nonspecific marker of tissue injury

Ramakant Rawat , Prasenjit Das, A K Dinda, S Datta Gupta, V Sreenivas, Vineet Ahuja, Sanjay K Aggrawal, Govind K Makharia

Departments of Gastroenterology and Human Nutrition, Pathology, Biostatistics and Nephrology, All India Institute of Medical Sciences, New Delhi 110 029, India

Introduction: Anti-tTG Ab immunohistochemistry stains has used as a marker of tissue involvement in celiac disease (CeD). An association between IgA nephropathy (IgAN) and CeD has been proposed but evidences are scarce. In order to establish an association between IgA nephropathy and CeD, we immunostained renal biopsies of IgAN, other nephropathies and biopsies from other organs with anti-tTG Ab.

Materials and Methods: Tissue blocks of patients with IgAN (n=105), minimal change disease (n=15), membranous glomerulonephritis, renal cell carcinoma and membranoproliferative glomerulonephritis and other tissues including liver biopsies from ALF, intestinal biopsies from CeD and tropical sprue and colonic biopsies IBD were retrieved and sections were immunostained with anti-tTG2 Ab. After staining, slides were read for intensity and distribution of stain. Composite score were generated as a multiple of intensity and distribution scores.

Result: Compared to control biopsies, both IgAN (673±482 vs. 136±84, p=0.02) and other nephropathies (710±435 vs. 136±84, p=.008) had significantly higher anti-tTG ab staining scores. There was no difference in composite scores of anti-tTG Ab stain in IgAN in comparison to other nephropathies (673±482 vs. 710±435, p=.5). Even liver biopsies from chronic hepatitis B and C, intestinal biopsies from CeD and tropical sprue and colonic biopsies from IBD showed staining with anti-tTG antibody. There was no difference in IgA anti-tTG ab staining score in other diseases such as ALF, IBD and TS in comparison to CeD.

Conclusion: Anti-tTG2 antibody immunohistochemical staining is a non-specific marker of tissue injury and not specific marker for CeD.

LI-21

Toll like receptors 4 and 5 but not 2 mRNAs are over-expressed in colonic biopsy among patients with irritable bowel syndrome

Ujjala Ghoshal , Ratnakar Shukla, Vikas Agarwal 1 , Tapan N Dhole, Uday C Ghoshal 2

Departments of Microbiology, 1Immunology, and 2Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014, India

Background: Evidence of low grade inflammation, increased intestinal permeability and altered host-microbial interactions suggests that innate immune response may play an imperative role in the pathogenesis of irritable bowel syndrome (IBS), hitherto an enigmatic disorder. Since toll like receptors (TLRs) are important component of innate immune system. We aimed of study TLR-2, TLR-4 and TLR-5 expression in colonic biopsies among patients with IBS.

Methods: Quantitative real-time PCR was used to determine the relative expression of mRNA of TLRs in colonic biopsy samples in 47 patients with IBS (Rome III criteria) and 30 controls.

Results: Of 47 patients with IBS (comparable in age and gender with controls), 20 had constipation (IBS-C), 20 had diarrhea (IBS-D) predominant IBS; the syndrome could not be sub-typed (IBS-U) in 7 using Rome III criteria. Relative expression of TLR-4 and TLR-5 was up-regulated in patients with IBS compared to controls (TLR-4: [0.15±0.06] vs. [0.002±0.001], p<0.001; TLR-5: [3.14±1.02] vs. [0.05±0.17], p<0.001). Expression of TLR-4 and TLR-5 was higher both among IBS-C and IBS-D as compared to controls (p<0.001). Expression of TLR-2, however, was comparable ([0.06±0.006) vs. [0.05±0.010], p=0.089).

Conclusion: Up-regulations of TLR-4 and TLR-5 in colonic biopsies among patients with IBS may suggest that innate immune response may play a potential role in the pathophysiology of IBS.

LI-22

Quantitative determination of selected fecal microbiota in patients with irritable bowel syndrome and healthy controls: An evidence of dysbiosis

Ratnakar Shukla , Ujjala Ghoshal, Vikas Agarwal 1 , Tapan N Dhole, Uday C Ghoshal 2

Departments of Microbiology, 1Immunology, and 2Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014, India

Background: Dysbiosis may play role in IBS, hitherto an enigmatic disorder. We evaluated selected fecal microbes in IBS patients and healthy controls (HC).

Methods: Fecal 16S rRNA copy number of selected bacteria was studied using qPCR in 47 patients with IBS (Rome III) and 30 HC.

Results: Of 47 patients, 20 had constipation (IBS-C), 20 diarrhea (IBS-D) and 7 un-classified IBS (IBS-U). Relative difference in 16S rRNA copy number of Bifidobacterium (p=0.04) was lower while Ruminococcus productus-Clostridium coccoides (p=0.02), Veillonella (p<0.01), Bacteroides thetaiotamicron (p<0.001), Pseudomonas aeruginosa (p<0.001) and Gram negative bacteria (p<0.01) higher among IBS patients than HC. Number of Lactobacillus (p<0.01) was lower while Bacteroides thetaiotamicron (p<0.001) and segmented filamentous bacteria (SFB, p=0.01) higher among IBS-D than IBS-C. Numbers of Bacteroides thetaiotamicron (p<0.001), Pseudomonas aeruginosa (p<0.001) and Gram negative bacteria (p<0.01) were higher among IBS-C and IBS-D than HC. Quantity of SFB was higher among IBS-D (p<0.001) and lower among IBS-C (p<0.01) than HC. Number of Veillonella species was higher among IBS-C than HC (p<0.01). Pseudomonas aeruginosa was frequently detected among IBS than HC (46/47 [97.9 %] vs. 10/30 [33.3 %], p<0.001). Higher number of Bacteroides thetaiotamicron, Clostridium coccoides, Pseudomonas aeruginosa, Gram negative and SFB was associated with visible abdominal distension and Clostridium coccoides and Gram negative bacteria with bloating. Microbial flora was different among IBS than HC on principal component analysis.

Conclusion: Fecal microbiota was different among IBS than HC and different sub-types were associated with different microbiota. Pseudomonas aeruginosa was more frequent and higher in number among IBS patients.

LI-23

Polyposis in a family

V Saravanan

Madras Medical College, Chennai 600 003, India

LI-24

Does fecal calprotectin predict relapse of ulcerative colitis?

Alok Sangam , A S Puri

G B Pant Hospital, J L Nehru Marg, New Delhi 110 002, India

Background: Although colonoscopy is gold standard for disease activity, noninvasive markers like fecal calprotectin are being considered as a substitute for colonoscopy. In this study, we attempted to study whether fecal calprotectin estimation in patients with UC during remission could predict a relapse in future.

Methods: Total 101 patients of ulcerative colitis were evaluated. Five patients were excluded. All these patients were evaluated for active disease or remission on basis of partial MAYO score. Patients with Mayo score ≤2 was subjected to FCP estimation by ELISA method colonoscopy and fecal calprotectin estimation were performed in all patients. Colonoscopy and FCP were performed subsequent two week to correlate with endoscopic activity. Correlation analysis was done with Pearson statistics.

Results: Mean age of presentation was 31 year. Sixty percent patients were male. Extent of disease in form of E1/E2/E3 was 61 %, 27 % and 12 % respectively. Ninety-seven percent of patients were on mesalamine, 35 % on steroid and 29 % on azathioprine. Mean value of FCP in the patients with remission was 46 μg/g where as in those patients with active disease, it was 694 μg/g. Ten patients, in whom Mayo score ≤2 had value of FCP ranging between 76-1556 μg/g (median-556). Each of these patients was followed up for a median period of 18 month (12-28 months), without any change in existing treatment. None of these 10 patients had relapse over 12-28 months (median-18 month).

Conclusion: Whereas FCP values differentiate active and remission phase of disease, they are poor predictor of future relapse.

LI-25

Retrospective and prospective study of inflammatory bowel disease from a south Indian referral centre for 4 years

K Veeraraghavan , M Kani Sheikh, R Kini, K Prem Kumar, T Pugazhendhi, Mohammed Ali

Department of Medical Gastroenterology, Madras Medical College, Chennai 600 003, India

Background: Inflammatory bowel disease (IBD) occurs worldwide. It is considered common most in Europe and North America and uncommon in most of develo** Asian countries. The incidence and prevalence of IBD varies not only among geographic region but also with race and ethinicty. There are limited data on epidemiology of IBD from India.

Aim: To determine the distribution and prevalence of IBD among patients attending Madras Medical College Hospital (South Indian tertiary referral centre) from 2010 to 2014.

Materials and Methods: Patients having complaints of chronic diarrhea underwent colonoscopy. Those found to have endoscopic criteria for IBD were taken biopsy from 10 different quadrants including both abnormal and normal areas of colonic and distal ileal mucosa. They were analyzed according to mean age, sex predilection, symptomatology, various types of IBD, subsite specificity, endoscopic grading of severity and histologic grading of ulcerative colitis (UC).

Observations: Among 425 patients who had chronic bloody diarrhea and underwent colonoscopy 210 patients had inflamed colonic and distal ileal mucosa. Biopsy proven IBD was noticed in 144 patients in which 62 were females and 82 were males. The range of age was 20 to 35 years and 52 to 64 years. Most common symptom was chronic bloody diarrhea with tenesmus. Among 144 IBD patients 136 were having UC and 8 had Crohn’s disease. Among 136 UC patients 42 patients had pancolits, 40 had left sided colitis, 36 had proctitis and 18 had proctitis with distal ileitis (backwash ileitis). Interestingly 5 patients had dysplasia and 2 had adenocarcinoma. Among 8 CD patients 4 had skip lesions in colon with ileitis and duodenal involvement and 2 had fistulizing variety (multiple perianal fistulas) and 2 had fissuring variety. Average histologic severity index of UC among those patients were grade 5.

Conclusion: The present study had given the distribution and prevalence of IBD among chronic diarrhea patients from a tertiary care hospital setting. Interestingly 5 patients had been diagnosed at an earlier stage of carcinoma (dysplasia).

GI Motility

GIM-01

Beneficial effect of naloxone hydrochloride for the treatment of acute intestinal pseudoobstruction

Vijay Sharma * , Suresh Bhargawa #

Departments of Gastroenterology, and  Crical Care*,#, Soni Manipal Hospital, Sector 5, Main Sikar Road, Vidhyadhar Nagar, Jaipur 302 013, India

Background: In acute intestinal pseudoobstruction there is dilation of the intestinal loops without mechanical obstruction, it may develop after surgery or severe illness. This condition is due to an acute imbalance of the normal extrinsic autonomic innervation of the bowel. Although it may resolve with conservative therapy, colonoscopic decompression is sometimes needed to prevent ischemia and perforation of the bowel. Studies suggest that neostigmine is an effective treatment. However there is no reported experience from India with naloxone hydrochloride. Naloxone hydrochloride, an opiod antagonist, is a synthetic congener of oxymorphone.

Methods: We studied patients admitted in intensive care unit (ICU) fulfilling criteria of acute intestinal pseudoobstruction in the form of clinical abdominal distention and radiographic evidence of significant small bowel and colonic dilation. Reversible and mechenical causes of abdominal distenstion ruled out. When there was no response to at least 24 hours of conservative treatment, we prospectively recruited patients to receive 3.0 mg of naloxone (one ampule contains 0.4 mg, so seven and half ampule Inj naloxone) given through Ryle’s tube, Ryle’s tube clamped for one hour, medicine administered 6 hourly. A physician who was unaware of the patients’ treatment assignments recorded clinical response defined as evacuation of flatus or stool and a reduction in abdominal distention), abdominal circumference, and measurements of the small bowel and colon on radiographs. Patients who had no response to the initial dose were eligible to receive open-label naloxone 6 hours later and subsequent doses 6 hrly for 24 hrs.

Results: Twelve patients were included in study, six patients were having pneumonia, septicemia, three patients with pylenephritis, septicemia, one patient with cerebrovascular accident, intracranial bleed, one patient with subacute bacterial endocarditis, septicemia, and one with cirhosis liver. Eleven patients who received naloxone had early intestinal decompression in the form of passage of flatus, passage of motion, decrease in abdominal girth, significant decrease in bowel diameter on X-ray flat plate abdomen, improvement in clinical parameters especially respiratory rate, oxygen saturation. In one patient colonoscopic decompression and also Inj. Neostigmine 2 mg required. The median time to response was 4 hours (range, 2 to 12). Side effects of naloxone included tachycardia in two patients, rise in blood pressure, irritability in one patient each.

Conclusion: This initial observation suggests that Ryle’s tube administration of naloxone hydrochloride is beneficial and safe in the treatment of ICU admitted patients with acute intestinal pseudoobstruction.

GIM-02

Irritable bowel syndrome with predominant bloating have significantly higher incidence of small intestinal bacterial overgrowth

Anish Philip , A S Asif, **o Thomas, Madhavan Mukunda, Krishnadas Devadas, R Sobhana Devi

Department of Gastroenterology Government Medical College, Kottayam 686 008, India

Introduction: Abdominal bloating is a common symptom in irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) also presents with similar symptoms like bloating and diarrhea. SIBO has been proposed as an etiological factor in IBS, but the evidence is conflicting.

Aim: To study whether there is higher prevalence of SIBO in patients with IBS with predominant symptom of abdominal bloating compared to IBS without significant abdominal bloating.

Methods: Subjects with IBS as per the Rome III criteria with predominant symptom of abdominal bloating was taken as cases. They were compared to age and sex matched controls which consist of IBS patients without bloating. The presence of SIBO in each group was tested by lactulose hydrogen breath test. The clinical characteristics and proportion of SIBO in two groups were compared.

Results: Total number of patients was 60; 30 cases and 30 controls. The mean age was 43.7±12.5 years in cases and 41.6 ±13.3 years in controls; p=0.53. There were 21 males in cases and 23 males in controls: p=0.55. Duration of illness was comparable between the two groups; 27.60 ±28.45 months in cases and 40 ±34.7 months in controls; p=0.92. Four out of 30 patients had lactulose hydrogen breath test positivity in cases compared none of the patients in the control group, which showed a significant difference (p=0.04).

Conclusions: IBS patients with bloating have a higher incidence of SIBO than patients without bloating in this study.

GIM-03

Chicago classification parameters for upright and supine position in gastroesophageal reflux disease: A preliminary report

M Srinivas , Vijaya Srinivasan, V Jayanthi

Department of Gastroenterology, Global Health City, Chennai 600 100, India

Background: We observed that there were some differences in interpretation by Chicago classification (CC) in high resolution esophageal manometry (HREM) done in upright and supine postures among patients with dysphagia and gastroesophageal reflux disease (GERD). We therefore aimed to evaluate the differences in CC parameters for liquid swallows (atleast 5 x 5 mL water) in both positions for patients with GERD retrospectively.

Methods: Swallows of 21 patients (excluding achalasia on HREM) with GERD tested in upright and supine position (16-channel water perfused catheter) were analyzed for peristaltic breaks (S1, S2+S3), distal latency (DL), contractile front velocity (CFV), integrated relaxation pressure (IRP) and distal contractile integral (DCI). Comparison was made between values for each parameter by test posture. Statistical analyses: Wilcoxon Signed Rank Test; p< 0.05 significant.

Results (Table): Three hundred and eighty swallows were analyzed (divided equally between both postures). Overall, most parameters had mean values, irrespective of posture, within the normal CC range. The IRP (8.8±4.5 vs. 11.68±9.47; p<0.03) and DCI (1071.9±982.05 vs. 1325.02±1026; p<0.01) were significantly lower in upright compared to supine values. All the other parameters were similar in both postures. The large standard deviation for DCI was probably due to small sample size.

Table Comparison of various HREM parameters between upright and supine postures in GERD

Parameter

Upright

Supine

p

S1

2.8±4.7

2.5±4.5

0.778

S2+S3

2.1±5.9

2.5±8.6

0.318

DL

5.4±0.9

5.5±0.8

0.056

CFV

9.2±2.9

10.3±2.5

0.165

IRP

8.8±4.5

11.7±9.5

0.029

DCI

1071.9 ±982.0

1325.0 ±1026.0

0.001

Conclusions: Most parameters in our study were normal by CC values irrespective of posture suggesting the need to standardize normal values in the Indian context. Despite this, lower IRP and DCI among the upright refluxers suggests greater retrograde propulsion in them.

GIM-04

Experience of high-resolution esophageal manometry in a tertiary care university hospital in southern India: A retrospective study

Antony Raphel Joy , G Rajesh, S Ismail, S Shine, M Geetha, R N Harikumar, K Anoop, V P Bhanu, N Prem, R P Venu, V A Narayanan, V Balakrishnan

Department of Gastroenterology, Amrita Institute of Medical Sciences and Research Centre, AIMS Ponekkara PO, Kochi 682 041, India

Background: We studied spectrum of esophageal motor disorders over a 7 year period in a tertiary-care university hospital in South India.

Methods: In this retrospective study, we analyzed manometric data and records of patients who underwent esophageal manometry from January 2007 to December 2013. High-resolution esophageal manometry was performed using 16 channel water perfusion system using conventional criteria (Trace 1.2). Upper gastrointestinal endoscopy was performed in all patients and barium studies were performed when clinically indicated.

Results: There were 868 (463 males, 405 females) patients who underwent esophageal manometry from January 2007 to December 2013. In 465 (53.6 %) patients, indication for esophageal manometry was motor dysphagia. Other indications included persistent reflux symptoms in 297 (34.2 %), non-cardiac chest pain in 75 (8.6 %) and recurrent vomiting in 31 (3.6 %) patients. Findings included achalasia cardia in 219 (25 %), low LES pressures in 179 (20.6 %), nonspecific findings in 129 (14.9 %), nutcracker esophagus in 88 (10 %), aperistalsis with low LES pressures consistent with systemic sclerosis in 14 (1.6 %), isolated hypertensive LES in 8 (0.9 %), diffuse esophageal spasm in 5 (0.5 %), and normal in 226 (26 %) patients. Of 465 patients with dysphagia, achalasia cardia was most common diagnosis. The most common cause of non-cardiac chest pain was nutcracker esophagus. The most common manometric finding in patients with reflux symptoms was low LES pressures with focal failure of peristalsis.

Conclusion: Classical achalasia cardia was most common cause of motor dysphagia while nutcracker esophagus was most common finding in non-cardiac chest pain.

GIM-05

Gastrointestinal manifestations of systemic sclerosis-Clinical and investigative study of 50 patients

M B Adarsh * , Rakesh Kochhar # , Saroj K Sinha # , Shefali Khanna Sharma * , Anish Bhattacharya, Satyavati Rana # , Surjit Singh *

Departments of Internal Medicine*, Gastroenterology# and Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Systemic sclerosis (SSc) is known to involve the gastrointestinal (GI) system and can lead to multitude of problems predominantly affecting the GI motility.

Methods: It was a prospective, observational, single centre study of fifty consecutive patients with SSc who presented to our rheumatology clinic. Clinical profile of all the patients was noted. Thirty-five patients underwent esophagogastroduodenoscopy (UGIE), 31 underwent esophageal manometry, 37 underwent lactulose breath test to assess orocecal transit time (OCTT) and glucose breath test for detecting small intestinal bacterial overgrowth (SIBO) and 36 underwent gastric emptying scintigraphy to measure gastric emptying time.

Results: Skin manifestations were seen in all patients and GI involvement was seen in 98 % of patients, with common symptoms being regurgitation (78 %) and heartburn (76 %). In UGIE, esophagitis was seen in 30, of which 3 had candidiasis and 1 had HSV esophagitis. Two patients had gastric antral vascular ectasia. Hiatus hernia was noted in 10 patients. Mean lower esophageal sphincter pressure was 16.1±12.7 mmHg with hypotensive sphincter in twelve patients. Esophageal peristaltic abnormalities (aperistalsis or ineffective peristalsis) were observed in 90 % of 31 patients. Gastric emptying was delayed in 10/36 patients. OCTT was prolonged in 23/37 patients whereas SIBO was noted in 7/37.

Conclusion: The GI involvement is common in SSc with esophagus being the most commonly affected. Motility abnormalities make them prone for super added infections esp. infectious esophagitis and SIBO as observed in the study and should be investigated.

GIM-06

Reduction of breath methane using rifaximin shortens colon transit time and improves constipation: A randomized double-blind placebo controlled trial

Uday C Ghoshal , Deepakshi Srivastava, Asha Misra

Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Objective: Reducing methane may accelerate colon transit improving chronic constipation (CC). Accordingly, we evaluated rifaximin on slow transit CC associated with high methane.

Method: Bristol stool forms, frequency, colon transit time (CTT) and breath methane were evaluated in 23 patients with CC (Rome III), and methane production compared with 68 non-constipating IBS (NC-IBS). Methane-producing CC (basal >10PPM and/or post-lactulose >10PPM above basal) were randomized (double-blind) to rifaximin or placebo (thrice/day, 14 days). Post-treatment stool forms, frequency, breath methane and CTT were evaluated.

Results: CC tended to be methane-producers (13/23[56.5 %] vs. 25/68[36.5 %]; p=0.07) with higher area-under-curve (AUC) (2415[435-23580] vs. 1335[0-6562.5], p=0.021) than NC-IBS. 8/13 (61.5 %) methane-producers and 5/10 (50 %) methane non-producers had abnormal CTT (36-h marker retention: 53[0-60] vs. 19[8-56], p=0.062; 60-h: 16[0-57] vs. 13[3-56], p=0.877). Of 13 methane-producers, 6 (46.2 %) received rifaximin and 7 (53.8 %) placebo. After 1 month, AUC for methane was lower with rifaximin (6697.5[1777.5-23580] vs. 2617.5[562.5-19867.5], p=0.005) than placebo (3945[2415-12952.5] vs. 3720[502.5-9210, p=0.118). CTT normalized in 4/6 (66.7 %) on rifaximin (36-h marker retention: Fifty-four [44-57] vs. 36[23-60], p=0.05; 60-h: 45[3-57] vs. 14[11-51], p=0.09) but none with placebo (p=0.02) (36-h: 31[0-60] vs. 25[0-45], p=0.078; 60-h: 6[0-54] vs. 12[0-28], p=0.2). Weekly stool frequency (pre-treatment: 3[1-9] vs. post-treatment: 7 [1-14], p=0.05) and forms (type I: 2/6[33.3 %], II: 1/6[16.6 %], III: 3/6[50 %] vs. type I: 1/6[16.6 %], III: 3/6[50 %], IV: 1/6[16.6 %], V: 1/6[16.6 %]) improved with rifaximin than with placebo (7[3-21] vs. 7[1-14], p=0.08 and type I:1/7[14.3 %], II:1/7[14.3 %], III:1/7[14.3 %], IV:4/7[57.1 %] vs. type I:1/7[14.3 %], II:2/7 [28.6 %], III:1/7[14.3 %], IV:3/7 [42.8 %]).

Conclusion: Rifaximin improves constipation by reducing breath methane and transit.

Liver-Portal Hypertension

LPH-01

QT interval prolongation: A risk factor for development of hepatorenal syndrome in cirrhotic patients with acute variceal bleeding

George Peter , Paul Cheruvathoor George, Mashhood Padincharepurathu Villyoth, Suthanu Bahuleyan, Tony Joseph, K S Prasanth, Premalatha Narayanan, Kattoor Ramakrishnan Vinayakumar

Department of Medical Gastroenterology, Super Specialty Block-3rd Floor (SSB -3), Government Medical College, Thiruvananthapuram 695 011, India

Background: This study aims to assess whether QT interval prolongation is an independent risk factor for development of hepatorenal syndrome (HRS) in cirrhotic patients with acute variceal bleeding.

Methods: Seventy-eight consecutive cirrhotic patients with acute variceal bleeding were included in the study. All patients were evaluated before bleeding (T0), during bleeding (T1) and 6 weeks later (T2).

Results: Development of HRS was observed in 14 (17.9 %) patients. QT corrected by heart rate (QTc) prolonged at T1, returning towards baseline at T2 (mean±SD; from 424.0 ±10.2 to 461.2±17.6 to 426.1±8.8 ms, p<0.001). At T1, patients who developed HRS had longer QTc (p=0.017) and lower serum sodium (p=0.039). QTc and serum sodium independently predicted HRS; the best cut-off values were QTc ≥468 ms and sodium ≤120 mEq/L. Patients on beta blocker were found to have a significant risk for develo** HRS (p=0.040). Based on these three factors, the risk for HRS was 0 % for patients without risk factors, and 6.1 %, 11.1 %, and 83.3 % for those with one, two and three risk factors respectively (p<0.001).

Conclusions: Acute variceal bleeding causes further prolongation of QTc in cirrhosis. The combination of use of beta blocker, QTc interval and serum sodium can aid in early detection of patients at increased risk of develo** bleed-precipitated HRS, thus improving their outcome.

LPH-02

WITHDRAWN

LPH-03

Diagnostic accuracy and clinical significance of cystatin C as a marker of renal function in cirrhosis

Deepakkumar Gupta , Rajiv Baijal, H R Praveenkumar, Deepak Amarapurkar

Jagjivan Ram Railway Hospital, Maratha Mandir Marg, Behind Maratha Mandir Cinema, Mumbai Central, Mumbai 400 008, India

Aim: To compare the diagnostic accuracy and clinical significance of cystatin C in cirrhotic patients with normal creatinine and patients who developed acute kidney injury on follow up.

Methods: A prospective cohort analysis of cirrhotic patients having normal serum creatinine was performed. Measurement of baseline glomerular filtration rate using cystatin C and creatinine based formulae was compared with DTPA scan. Patients were followed up for 12 months for development of acute kidney injury and retrospective analysis of baseline parameters was performed for predictors of acute kidney injury.

Results: Ninety-eight patients of cirrhosis with normal serum creatinine level (<1.2 mg/dL) constituted the study population. On comparison with 99Tc DTPA estimated GFR; cystatin C based formulae had better accuracy and lesser bias as compared to creatinine based formulae of GFR. Cystatin C was the only independent factor predicting renal impairment (GFR <60) inspite of normal serum creatinine. Chronic kidney disease (CKD) combine formula was the best among all GFR formula in detection of renal impairement. On follow up for 12 months, forty-one (41.8 %) patients developed acute kidney injury and twenty-eight patients (28.5 %) expired. On regression analysis cystatin C was a significant predictor of acute kidney injury with hazard ratio of 2.35 with a cut-off of 1.04 of cystatin C. Cystatin C was higher in expired patients as compared to serum creatinine. However, it was not significant in multivariate analysis.

Conclusion: Serum cystatin C based formulae showed a better diagnostic accuracy in estimating renal impairement than serum Cr based formulae when compared with 99mTc DTPA scan determined GFR. Cystatin C can be a predictor of AKI which can help in early intervention in high risk patients.

LPH-04

Impact of bisphosphonate supplementation in patients with osteoporosis secondary to non-choleastatic liver cirrhosis

Rinkesh Kumar Bansal, Piyush Ranjan, Vinit Shah, Mandhir Kumar, Munish Sachdeva

Sir Ganga Ram Hospital, Old Rajender Nagar, New Delhi 110 060, India

Background and Objectives: Patients with liver cirrhosis are more prone to develop bone disease i.e. hepatic osteodystrophy (HOD). Treatment of HOD has not been standardized; calcium and vitamin D supplementation alone are not helpful.

Aim: Aim of this study was to determine impact of bisphosphonates in patients with osteoporosis in non- choleastatic liver cirrhosis.

Methods: Consecutive patients with liver cirrhosis admitted at Sir Ganga Ram Hospital, Delhi between 2012-2013 were enrolled. Bone mineral density was measured by DEXA at the lumbar spine. Oral bisphosphonate i.e. Ibandronate 150 mg once a month was given in patients with osteoporosis and DEXA scan along with baseline investigations were repeated after 6 months.

Results: Total 215 patients with liver cirrhosis were enrolled. HOD were found in 142 (66 %), out of which 47 had osteoporosis. Out of 47 osteoporotic individuals, 34 % (n-16) died and 26 % (n-12) were lost to follow up. Forty percent (n-19) completed the treatment and were followed up after 6 months and assigned as treatment group. Nineteen patients (male-18) with mean age 50.9±11 years were analyzed. Serum calcium and vitamin D significantly improved in treatment group in comparison to baseline. BMD and t-score also improved significantly. No significant adverse events related to drugs were noted.

Conclusions: This is the only Indian study on role of oral bisphosphonate in osteoporosis in patients with liver disease. Being oral, once a month and very less adverse effects, Ibandronic acid is a very good drug in osteoporosis in patients with liver disease.

LPH-05

Prevalence of minimal hepatic encephalopathy in cirrhosis of liver by psychometric tests

S Ramakanth , P Shravan Kumar, M Umadevi , M Ramanna

Department of Gastroenterology, Gandhi Medical College, Secunderabad 500 025, India

Aim and Objectives: To study the prevalence of minimal hepatic encephalopathy (MHE) in cirrhosis of liver patients (COL) in a tertiary care centre by psychometric tests.

Methods: Thirty patients of COL attending gastroenterology are evaluated for MHE after satisfying inclusion exclusion criteria. Exclusion criteria: overt hepatic encephalopathy (HE), history of HE, intake of psychotropic drugs, alcohol in <6 weeks, severe electrolyte disturbances, sepsis, severe cardiac or renal impairment, severe neurological or psychiatric disorder. Assessment of patient education, Child-Pugh class, etiology of cirrhosis done. All patients are subjected to 5 psychometric tests which include 1) number connection test- A 2) number connection test-B 3) digit symbol test 4) serial dotting test 5) line tracing test. Results are obtained from normality tables as SD from normal for each test. Test values are added. Total values <-4 are considered as diagnostic of MHE.

Results: Out of 30 patients 20 males (66 %) 10 females (33 %) mean age -41 yrs (18 yrs-65 yrs). Child class A – 15 (50 %) patients, Child class-B-13 (43 %) patients, Child class C-2 patients (7 %). Etiology: alcohol-12 (40 %), cryptogenic-8 (27.5 %), autoimmune-2 (6 %) HBV-4 HCV -2 chronic Budd-Chiari-1 NAFLD -1 are observed. Of total 30 patients, 17 patients showed evidence of MHE (57 %) on analysis Child class A - 6 patients (40 %) had MHE Child class B - 9 patients (68 %) had MHE Child class C -2 patients (100 %) had MHE.

Conclusions: Prevalence of minimal hepatic encephalopathy in cirrhosis of liver in this study was 57 % indicating a very high prevalence.

LPH-06

Clinical and laboratory profile of Type-1 hepatorenal syndrome

S Ramakanth , P Shravankumar, M Umadevi, M Ramanna

Department of Gastroenterology, Gandhi Medical College, Secunderabad 500 025, India

Aim: To study the clinical and laboratory profile of type 1 hepatorenal syndrome patients admitted into LICU of tertiary care centre.

Material and Methods: This is a retrospective study of all patients admitted into LICU during a period of September 2013 to June-2014. Type 1 hepatorenal syndrome was defined as per international ascities club consensus workshop 2007 criteria. All the patients are managed conservatively with IV albumin 1 g/kg bodyweight and IV Terlipressin. Clinical profile and mean laboratory values and prognostic factors was calculated. Profile of patients died in hospital and patients discharged were compared.

Results: Of total 20 patients - males -16 (80 %) females 4 (20 %), mean age 46.75 (25-60 yrs). Most common etiology of liver disease is alcohol related in -14 (70 %) followed by hepatitis B related -3, cryptogenic -2 both HBV and alcohol related in 1 hepatic encephalopathy was present in 16 patients (80 %) and upper gastrointestinal bleeding was present in 7 (35 %). All parameters are compared between, two groups: Group A (in hospital death group) – 8, group B (patients discharged from hospital) – 12.

Sl.no

Parameter

Total group (20)

A In hospital death group (8)

B Alive group (12)

1

Upper gastrointestinal bleed

7 (35 %)

6 (75 %)

1 (8.5 %)

2

Hepatic encephalopathy

16 (80 %)

8 (100 %)

8 (66 %)

3

Mean admission serum creatinine (mg/dL)

2.6

3.1

2.25

4

Mean serum sodium (meq/L)

128

122

132

5

Mean serum bilirubin (mg/dL)

8.9

12

6.7

6

Child-Pugh class

Class B 5

Class C 15

Class B -1

Class C- 7

Class B -8

Class C- 4

6

Mean MELD score

28.5

32.3

25

8

Mean MELD Na

31.25

35.5

28.2

7

Mean hospital stay

12 days

9.5 days

13.6 days

Conclusions : Type 1 hepatorenal syndrome was seen in those with high serum bilirubin, Child class B and C and high MELD score-28.5 and low serum sodium <128. Presence of UGI bleed, high serum bilirubin, low serum sodium, high MELD score predicted high short-term mortality of patients with type 1 hepatorenal syndrome.

LPH-07

Serum interleukin 8 and 12 levels predict severity and mortality in patients with alcoholic hepatitis

Onkar Prasad Patel , Mohd Talha Noor, Bhagwan Singh Thakur

Department of Gastroenterology, Sri Aurobindo Institute of Medical Sciences, Indore 543 111, India

Background: Alcoholic hepatitis (AH) is a common life threatening illness particularly when it is severe. Alcoholic liver disease is associated with cytokine imbalance. There is paucity of information about the relationship of interleukin (IL) levels with severity and mortality of patients with AH. Our aim was to correlate serum IL-8 and IL-12 values with disease severity (mild vs. severe) and mortality.

Methods: Fifty patients and twenty-five healthy subjects were included in the study. Serum IL-8 and IL-12 levels were analyzed and correlated with disease severity and mortality. Predictive value for 6 months mortality of IL-8, IL-12, Maddreys discriminant function (mDF), age, bilirubin, international normalized ratio (INR) and creatnine score (ABIC) and Glasgow alcoholic hepatitis score (GAHS) was compared by the area under the receiver operating curve (AUROC).

Results: Mean serum IL-8 levels were significantly higher in patients with severe AH as compared to mild AH [539.04±89.77 pg/mL vs. 253.66±56.66 pg/mL (p< 0.001)] and controls [539.04±89.77 pg/mL vs. 99.96±20.94 pg/mL (p<0.001)]. Similarly, mean serum IL-12 levels in severe AH was also significantly higher as compared to mild AH [344.47±93.04 pg/mL vs. 101.92±16.70 pg/mL (p<0.001)] and controls [344.47±93.04 pg/mL vs. 47.84±11.22 pg/mL (p<0.001)]. AUROCs of IL-8, IL-12, mDF, ABIC, and GAHS were 0.995, 0.998, 0.975, 0.873 and 0.883 for predicting 6 months mortality.

Conclusion: Serum IL-8 and 12 levels were markedly elevated in alcoholic hepatitis with increasing levels as the severity increases. Serum levels of IL-8 and 12 were better predictors of short-term mortality as compared to conventional prognostic scores.

LPH-08

Evaluation of vitamin D and calcium status in patients with cirrhosis of liver

Ravikant Kumar , Sri Prakash Misra, Manisha Dwivedi, Kailash Mishra, Pavan Kumar, Kandarp Nath Saxena

Department of Gastroenterology, Moti Lal Nehru Medical College, University of Allahabad, Allahabad 211 001, India

Introduction: Liver plays pivotal role in metabolism of vitamin D as it undergoes 25-hydroxylation reaction in it. Some studies have suggested that cirrhosis of liver is a risk factor for vitamin D deficiency and thus disrupts calcium homeostasis.

Aims: To determine the prevalence of vitamin D deficiency in patients with cirrhosis of varying etiology and its relationship to etiology and severity of cirrhosis of liver.

Methods: One hundred and sixty consecutive patients with cirrhosis of liver attending Swaroop Rani Nehru Hospital had been evaluated and their 25-hydroxyvitamin D level measured. Vitamin D was graded as optimum (30-100 ng/mL), deficiency (less than or equal to 20 ng/mL) and insufficiency (21-29 ng/mL).

Results: Of patients, 124/160 (77.5 %) had vitamin D deficiency/insufficiency. In alcoholic cirrhosis group, 50 % (28/56) had vitamin D deficiency and 28.5 % (16/56) had insufficient vitamin D. All eight patients of autoimmune hepatitis had non optimum vitamin D level. Sixty out of 76 patients (78 %) in CTP class C had vitamin D deficiency and was significantly more common than CTP class A/B.

Conclusion: Vitamin D deficiency is highly prevalent in cirrhosis of liver (77.5 %) and is positively related to severity of liver disfunction.

LPH-09

Impact of severity of acute kidney injury on mortality in hospitalized patients with decompensated cirrhosis

Prasanth K Sobhan , A B Suthanu, Tony Joseph, P V Mashhood, Paul Cheruvathur, George Peter, N Premaletha, K R Vinayakumar

Government Medical College, Thiruvananthapuram 695 011, India

Background: Although much attention has been devoted to eliciting risk factors for the development of acute kidney injury (AKI) in cirrhosis, few studies have explored survival outcomes.

Aim: To evaluate the impact of AKI severity on mortality in hospitalized patients with decompensated cirrhosis.

Materials and Methods: Decompensated cirrhosis patients with documented baseline serum creatinine (S.Cr) who developed AKI during November 2012 to April 2014 were included in this observational study. CKD and HCC excluded. AKI was defined as S.Cr more than or equal to 1.5 mg/dL. AKIN criteria was used for staging the severity. Patients were treated with human albumin 1 gm/kg/day for 48 hrs and response was assessed. Patients with HRS were managed with albumin and terlipressin. Patients were observed for in- hospital survival outcomes.

Results: Of 171 patients, 109 were enrolled and 37 (33.95 %) expired. Break-up based on AKIN criteria: AKI stage 1 (44.95 %); stage 2 (30.33 %); stage 3 (24.77 %). Mortality: AKI stage 1(21.21 %); stage 2 (24.48 %) and stage 3 (66.67 %). Univariate analysis: MELD score, S. Na, S. Cr at enrolment showed significant correlation with mortality (p<0.05). On Logistic regression: MELD (OR- 0.77, p-0.0001) S. Na (OR- 0.27, p-0.04).

Conclusion: AKIN staging correlated with mortality in hospitalized patients with decompensated cirrhosis. MELD and Na levels showed significant correlation with mortality.

LPH-10

Changes in gut microbiome in patients with liver cirrhosis

Amit Goel , Aditya N Sarangi, Ankur Singh, S Avani, Rakesh Aggarwal

Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Objective: Recent studies have shown alterations in gut flora in patients with liver cirrhosis (LC). However, more data on the subject are needed.

Methods: Morning stool specimens from 7 healthy adults (median age: 48 [44-56] years; 5 male) and 24 patients with LC (42 [30-65] years; 17 male; Child-Pugh A 5, B 15, C 4) were processed for DNA extraction, amplification of V3 region of bacterial 16S rRNA, and next-generation sequencing of the DNA library so generated. From sequencing data, operational taxonomic units (OTUs) were assigned by comparison with Greengenes database. For OTUs accounting for ≥0.005 % of total sequences in either group, abundances were compared between groups using Mann-Whitney U test with Benjimini-Hochberg correction. Persons receiving probiotics, antibiotics, or drugs likely to affect gut flora or motility, and those with gastrointestinal disease or diabetes were excluded.

Results: The 31 specimens yielded a mean of 695,543±257,059 high-quality reads each. These belonged to 17,716 OTUs, of which 562 accounted for >0.005 % of reads in at least one group. Phylums Bacteroidetes (59.7±14.1 % vs. 65.2±23.1 %), Firmicutes (27.2±10.4 % vs. 24.3±14.6 %) and Proteobacteria (11.7±5.5 % vs. 8.0±10.9 %) had similar mean abundances in controls and LC. Abundances of 2 classes (RF3 in phylum Tenericutes, Deltaproteobacteria in phylum Proteobacteria), 6 orders (Aeromonadales, Oceanospirillales, Desulfovibrionales and Pasteurellales in Proteobacteria, and ML615J-28 and RF39 in Ternicutes), 6 families (including 3 in Proteobacteria, 1 in Firmicutes and 2 in Tenericutes), and 6 genera and various measures of flora diversity differed significantly (p<0.05) between LC and controls.

Conclusion: Patients with LC show differences in gut flora compared to healthy controls. These differences may have a pathogenetic role in causation of LC or its complications.

LPH-11

A study of prevalence of insulin resistance and impaired glucose tolerance in patients with chronic liver disease- A pilot study from south India

S Sukumaran , K Muthukumaran, G Ramkumar, R Balamurali, T Raj Kumar Solomon, A Murali, P Ganesh

Department of Digestive Health and Diseases, Kilpauk Medical College, Chennai 600 010, India

Introduction: Diabetes that develops as complication of cirrhosis is known as -hepatogenous diabetes (HD). Around 30 % to 60 % of cirrhotic patients suffer from HD. In chronic liver disease (CLD), the metabolic homeostasis of glucose is impaired because of IR and impaired sensitivity of islet Î2-cells in the pancreas. HD in early cirrhosis may be sub-clinical. Only insulin resistance (IR) and impaired glucose tolerance (IGT) by an OGTT may be observed. As liver disease advances, diabetes becomes clinically manifest, therefore HD may be considered as a marker for liver function deterioration.

Aim: 1. To estimate IR by HOMA score and IGT by OGTT with 75 g glucose in patients with CLD. 2. To identify patients with risk of develo** HD in patients with CLD’

Materials and Methods: This is an ongoing prospective study in our department from January 2014. Patients with CLD were included in the study. Patients with diabetes, family history of diabetes and RBS >140 mg/dL were excluded. Each patient evaluated with fasting insulin level, FBS and second hour PPBS by OGTT with 75 g glucose.

Results: So far 30 patients (25 males and 5 females) were included. Six patients (20 %) had insulin resistance (moderate-3, severe-3), 16 patients (53 %) had IGT. IGT is more common in patients with CTP B (5 patients-31 %), CTP C (8 patients-50 %) and MELD score->15 (9 patients-56 %).

Conclusion: With the available preliminary data, the prevalence of insulin resistance and IGT in patients with CLD was 20 % and 53 % respectively. IGT is found more commonly in those patients with CTP score B, C and high MELD score.

LPH-12

Study of portal hypertensive gastropathy and duodenopathy in decompensated cirrhotic patients

A Anand, K Muthukumran, G Ramkumar, R Balamurali, T Rajkumar Solomon, P Ganesh

Department of Digestive Health and Diseases, Government Kilpauk Medical College, Chennai 600 010, India

Aim: To study of prevalence of portal hypertensive gastropathy (PHG) and portal hypertensive duodenopathy (PHD) in decompensated cirrhotic patients and its correlation with severity of the disease.

Materials and Methods: One hundred and ten decompensated cirrhotic patients who first time underwent upper gastrointestinal endoscopy were included in the study. Patients with previous endoscopic band ligation and sclerotherapy were excluded. The prevalence of PHG and PHD were noted and correlated with Child-Pugh scoring.

Results: PHG was present in 56 % (62 patients) and PHD was present in 5 % (6 patients) and both PHG and PHD was present in 10 % (11 patients). Mild PHG was present in 84 % (52 patients) and severe PHG was present in 16 % (10 patients). Esophageal varices was present in (50 of 62; 81 %) and esophagogastric varices (12 of 62; 19 %) of the patients with PHG. Out of the 6 patients with PHD, 4 patients had esophagogastric varices (67 %) and 2 patients had esophageal varices (33 %). PHG was present more in Grade-2 esophageal varices (73 %) and PHD was present more in Grade-3 esophageal varices (83 %). Prevalence of mild PHG was 15 % in CTP A; 52 % in CTP B; 33 % in CTP C and severe PHG was 20 % in CTP B; 80 % in CTP C. Prevalence of PHD was 33 % in CTP B; 67 % in CTP C.

Conclusion: This study demonstrated that PHG is more frequent than PHD in patients with decompensated cirrhotic patients. PHD occurs more in patients with esophagogastric varices. Prevalence of severe PHG and PHD is higher in Child-Class C.

LPH-13

Study of adrenal insufficiency in patients with cirrhosis of liver

Balaji Gurappa , Santhi  Selvi, P Ganesh, T S Rajkumar, R Balamurali, G Ramkumar, K Muthukumar

Department of Digestive Health and Diseases, Kilpauk Medical College, Chennai 600 010, India

Introduction: The liver is one of the most vital organ sub serving several important functions such as synthesis, storage and metabolism. Liver is the primary site of metabolism of adrenal steroid hormones. Adrenal dysfunction has been reported in the spectrum of disease ranging from compensated to liver failure.

Aim: To assess the prevalence of adrenal insufficiency and correlate with disease severity in patients with chronic liver disease.

Materials and Methods: One year prospective, observational study (January 2013 to January 2014). One hundred patients were enrolled in the study. 8 a.m serum cortisol levels were measured for all patients.

Results: Of 100, 29 % had low serum cortisol levels (<5 mcg/dL). Among the 83 patients with hyperbilirubinemia, 29 (34.9 %) patients had adrenal insufficiency (p.value 0.004). On correlating with CTP scores, none of the CTP-A (30) had adrenal insufficiency, whereas 10/35 (28.6 %) of CTP-B and 19/35 (54.3 %) patients with CTP-C had adrenal insufficiency (p.value <0.001). Among 13 patients with S albumin <2.0 g/dL, 11 patients (84.6 %) had adrenal insufficiency and S. albumin <2.0–2.5 g/dL, 15 patients (48.4 %) had adrenal insufficiency (p<0.001). Fourteen out of 31 (45.2 %) of UGI bleed had adrenal insufficiency (p. 0.017). Fifteen out of 39 (38.5 %) of hepatic encephalopathy (p. 0.095) and 16/29 (55.2 %) of hepatorenal syndrome had adrenal insufficiency respectively (p.<0.001).

Conclusion: Adrenal insufficiency occurs frequently in liver cirrhosis both during critical illness and in stable disease. Correlates well with disease severity and should be periodically assessed for adrenal insufficiency. Significant correlation was found between serum cortisol and serum bilirubin, variceal bleeding, CTP score, and hepatorenal syndrome.

LPH-14

Liver and spleen stiffness in patients with noncirrhotic portal hypertension

Sonali Gautam , Deepak Amarapurkar

Bombay Hospital and Medical Research Centre, 12, Marine Lines, Mumbai 400 020, India

Background and Aims: Noncirrhotic portal hypertension (NCPH) is considered as presinusoidal extrahepatic portal hypertension in the absence of fibrosis in the liver. We evaluated liver stiffness (LS) and spleen stiffness (SS), measured by acoustic radiation force impulse imaging (ARFI) in patients with NCPH and compared it with fibrosis in chronic liver diseases (CLD) and controls.

Material and Methods: A prospective study conducted at tertiary care centre, where we have evaluated 40 patients of NCPH (30 EHPVO and 10 of NCPF). LS and SS was measured by ARFI imaging and values were compared with 34 patients with F0 fibrosis in CLD and 67 healthy volunteers (controls).

Results: Out of 40 patients of NCPH (mean age 39.71±14.4 years, 14-77 years, 20 males, mean BMI 22.8 (±4.2) Kg/m2) had a mean LS(m/s), SS(m/s) and APRI of 1.7 (±0.5), 3.4 (±0.4) and 0.7 (±0.6). Similarly in CLD (n=31, F0) and controls the mean LS (m/s), SS(m/s) and APRI were 1.82 (±0.59), 2.66 (±0.56) and 1.4 (±1.73) and 1.41 (±0.26), 2.43 (±0.45) and 0.30 (±0.24) respectively. LS and APRI did not significantly differentiate NCPH from F0 (p=0.98, 0.95) and controls (p=0.15, 0.99) with LS and APRI higher in F0 than NCPH (1.82±0.59 vs. 1.7±0.5 and 1.4±1.73 vs. 0.70±0.6) and control (1.82±0.59 vs. 1.41±0.26 and 1.4±1.73 vs. 0.30±0.24). SS was significantly higher in NCPH than F0 (p<0.01) and controls (p<0.01).

Conclusion: SS is significantly higher in NCPH than F0 and control whereas LS and APRI is higher but not statistically significant in F0 than NCPH and control.

LPH-15

Measurement of liver and spleen stiffness by acoustic radiation force imaging identifies cirrhotic patients with esophageal varices

Sonali Gautam , Deepak Amarapurkar

Bombay Hospital and Medical Research Center, 12, Marine Lines, Mumbai 400 020, India

Background and Aims: Esophageal varices (EVs) resulting from portal hypertension (PHT), are evaluated with invasive esophagogastroduodenoscopy (EGD). We evaluated whether noninvasive methods like spleen (SS) or liver stiffness (LS), measured by ARFI imaging (mean, m/s) can identify patients who have EVs; those without EVs would not require endoscopic examination. It was compared with AST platelet ratio (APRI) scores.

Methods: Our study group had mean age 49 (±13.86) years, 162 males (M:F=2: 1) NAFLD as most common etiology, with mean SS, LS and APRI in controls as 2.43 (±0.45) m/s, 1.41 (±0.26) m/s and 0.30 (±0.24). In all cases diagnosed as cirrhosis with PHT (n=197; radiological and EVs), SS, LS and APRI was 3.10 (±0.49) m/s, 2.27 (±0.69) m/s, 1.44 (±1.27) respectively and SS was found to statistically significantly predict the presence of PHT (p=0.03) and EVs (p<0.005). Similarly, SS had high diagnostic performance for presence of significant EVs (F2 and F3; p=0.000184) and predict variceal bleeding (n=31, p<0.000248). Neither LS or APRI score could predict presence of PHT (p=0.094; p=0.609) and EVs (p=0.585; p=0.623) with none of the scores (SS,LS and APRI) predicting the progression of small to large EVs (p=0.88, 0.82 and 0.85 respectively).

Conclusions: Measurements of SS can be used to identify patients with presence of EVs or significant EVs with risk of variceal bleeding.

LPH-16

WITHDRAWN

LPH-17

To assess the utility of acoustic radiation force impulse imaging of liver and spleen in predicting the variceal status in chronic liver disease

B Harshavardhan Rao , I Siyad, G Rajesh, Rama P Venu, M Geetha, V P Bhanu, R Harikumar Nair, Anoop Koshy, Jeffey George, V A Narayanan, V Balakrishnan

Department of Gastroenterology, Amrita Institute of Medical Sciences and Research Centre, AIMS Ponekkara PO, Kochi 682 041, India

Background and Aim of the study: The development of portal hypertension is a common consequence of chronic liver diseases evidenced by invasive modalities like endoscopic visualization of esophageal varices and HVPG. This study explores acoustic radiation force impulse (ARFI) as a noninvasive modality to predict esophageal varices and thereby serve as an indirect marker of portal hypertension.

Material and Methods: This was an cross-sectional study where patients with a diagnosis of chronic liver disease of any etiology without hepatocellular carcinoma, Ascites or endoscopic variceal ligation/sclerotherapy; between January 2013 and December 2013 were included and ARFI was performed using a validated software.

Results: Sixty-seven patients were included with mean age of 52.04±11.316 years, a preponderance of males (83.6 %) with alcohol (53.7) being the most common etiology. Among the patients with esophageal varices (86.5 %), 35 patients (52.23 %) had small varices. Using a cut-off of 2.25 m/sec, liver stiffness exhibited a rather low sensitivity (75 %) for prediction of varices. Spleen stiffness (with a cut-off of 2.15 m/sec) however showed a statistically significant linear correlation with a sensitivity of 91.4 % and a positive predictive value of 98.1 % for the prediction of varices. Both liver and spleen stiffness showed a statistically significant correlation with the variceal grade (p- 0.01 and 0.00 respectively).

Conclusions: Liver and spleen stiffness were measured using ARFI elastography. Spleen stiffness measured by ARFI can be used as a noninvasive method for predicting the presence and size of varices. Liver stiffness however, had a significantly lower sensitivity and specificity for prediction of varices.

LPH-18

Endoscopic ligation compared with sclerotherapy for treatment of bleeding esophageal varices in decompensated cirrhotics

Pabitra Sahu, Premasish Kar, K Suresh Kumar

Department of Medicine, Maulana Azad Medical College, Bahadur Shah Zafar Marg, Delhi Gate, Delhi 110 002, India

Background: Acute variceal bleeding is a complication of liver cirrhosis and its most appropriate therapeutic approach is an issue of controversy. This study aims at comparing the efficacy of band ligation and sclerotherapy.

Methods: The study was a prospective randomized study where two groups, EVL and EST were comparable in etiology, severity of liver disease and grade of varices. Treatment was measured by initial control of bleeding, incidence of early or late bleeding, survival and complications. Therapies repeated at 3 weekly intervals until varices were reduced to grade 1 or eradicated.

Results: One hundred and eleven patients were randomly assigned to EVL group and 103 to EST group. The initial hemostasis rate was better in EST than EVL group (96 % vs. 94 %, p=ns). However, EST group required more therapeutic sessions (mean 5.8±2.1) to eradicate varices compared to EVL group (mean 4.4±1.6). Larger percentage of patients in EST group required blood transfusion during course of treatment and also had higher episodes of rebleed (26.2 %). Rebleeding in EVL group was significantly less (14.4 %). After a follow up period of 12 months eradication rate of varices in EVL group was higher at 86 % than EST (73 %). Bleeding related mortality was lower in EVL than EST group (7.2 % vs. 13.6 %).

Conclusions: EVL scored over EST in terms of eradication rate of varices and lesser number of complications and mortality. The probability of patients remaining free of bleeding was higher (p<0.01) in EVL group than EST group. Hence, EVL is faster and more effective option than ES for initial and long-term control of bleeding and is associated with low incidence of bleeding as well as other non-bleeding complications.

LPH-19

WITHDRAWN

LPH-20

Portal hypertensive biliopathy in extrahepatic portal vein obstruction

Suja K Geevarghese , Varghese Thomas

Department of Gastroenterology, Government Medical College, Calicut 673 008, India

Background: Extrahepatic portal vein obstruction (EHPVO) is not uncommon in India. Most of the EHPVO patients survives and grows into adulthood, but they may develop the rare complication of portal biliopathy.

Aim: To study occurrence and clinical features of portal biliopathy in a cohort of patients with EHPVO attending a tertiary care centre.

Methods: Sixty-one consecutive patients with EHPVO were studied. Detailed clinical evaluation was done in all. All patients had LFT, ultrasound abdomen and MRCP. The study was approved by institutional ethics committee.

Results: The split up of patients were as follows: Group I symptomatic patients (n=15), Group II asymptomatic patients with abnormal LFT (n=11), Group III asymptomatic patients with normal LFT (n=35). The male: female ratio was 8:7, 7:4, and 21:14 each group. Mean age was 38.67, 39.27, and 35.74 years respectively. Most common symptom was jaundice. Cholangitis was present in 2 (3.2 %) patients. Mean total and conjugated bilirubin were 5.2/2.12, 2.12/0.9, 0.94/0.4 mg/dL respectively. Mean SGPT (iu/m/) and ALP (iu/mL) were 38.53/329.07, 45.18/183.27 and 28.83/91.6 respectively. USG abnormality affecting biliary system was seen in nine (60 %), one (9.1 %) and two (5.7 %) patients respectively. MRCP was abnormal in fifteen (100 %), ten (90.9 %) and twenty-nine (82.9 %) patients respectively. Some evidence of portal biliopathy was present in 54/61 patients (88.5 %).

Conclusions: Mean total bilirubin, conjugated bilirubin, serum alkaline phosphatase levels were significantly higher in group I (symptomatic) compared to group III (asymptomatic) (p<0.05). Majority of portal hypertensive biliopathy (PHB) patients (75 %) were asymptomatic. But those with symptoms of biliary disease had a higher likelihood of having PHB (100 %).

LPH-21

Minimal hepatic encephalopathy in children with extrahepatic portal vein obstruction

K Raja Yogesh , Mohammed Ali, T Pugazhendhi, D Nirmala, Sumathy, Prem Kumar, Ratnakar Kini, Kani Shaikh

Madras Medical College, Chennai 600 003, India

Introduction: Extrahepatic portal vein obstruction is one of the vascular disorders of the liver. In children, it accounts for 70 % of cases of portal hypertension and is the commonest cause of upper gastrointestinal bleed. Minimal hepatic encephalopathy is said to exist in patients who appear clinically un-impaired but have abnormalities on psychometric testing. Though the presence of MHE has been demonstrated in adults with EHPVO, it’s occurrence in children has not been studied or established. This study aims to evaluate children with EHPVO for the existence of MHE.

Materials and Methods: Thirty children with EHPVO were taken as per the inclusion and exclusion criteria. They were subjected to psychometric tests namely - number connection tests, digit symbol test, serial dotting test, line tracing test and critical flicker frequency. Their scores were compared with the sores of age matched normal children and taken to be abnormal if they were >2 S.D above the mean of the controls. If a child with EHPVO had more than two abnormal tests, he was said to have MHE.

Results: Fifty percent of children showed abnormality in - 2 psychometric tests, suggesting minimal hepatic encephalopathy. Forty-six percent of children had an abnormal critical flicker test result. The CFF results correlated well with the psychometric test results.

Conclusion: MHE does exist in a large proportion of children with EHPVO based on psychometric tests and critical flicker frequency.

LPH-22

Acoustic radiation force impulse imaging: A noninvasive tool for prediction of esophageal varices in chronic liver disease

Sandeep J Patil , Ravi Shankar Bagepally, G R Srinivas Rao, D Viswanath Reddy, B Vamshi Krishna Reddy

Department of Gastroenterology, Yashoda Hospitals, Behind Hari Hara Kala Bhavan, S P Road, Secunderabad 500 003, India

Aims: We evaluated clinical utility of spleen stiffness (SS) by using acoustic radiation force impulse (ARFI) technology and compared these results with presence of esophageal varices and correlation with grades of esophageal varices. We also compared these values with liver stiffness (LS).

Methods: We measured SS and LS in 63 patients with cirrhosis at Yashoda Hospitals, Secunderabad. The diagnostic accuracy of SS for the presence of EVs was compared with that of LS. Optimal cut-off values of SS were chosen to assess high-grade EVs.

Results: Levels of SS were higher among patients with EVs than who do not have varices, and values were highest among patients with high-grade EVs. SS had the greatest diagnostic accuracy for the identification of patients with EVs/high-grade EVs compared with LS. An SS cut-off value of 2.7 m/s identified patients with EVs with 90 % positive predictive value, 72 % sensitivity, 69.23 % specificity, and 0.4 negative likelihood ratio. SS cut-off value of 3.20 m/s identified patients with high-grade EVs with 90.5 % negative predictive value, 73.33 % sensitivity, 79.17 % specificity, and 0.34 negative likelihood ratio. SS values less than 3.2 m/s is having low probability of high-grade varices in patients with cirrhosis. It is superior to liver stiffness for prediction of high grade varices.

Conclusions: Measurements of SS can be used to identify patients with cirrhosis with high-grade EVs. A cut-off SS was identified that could suggest low probability of high-grade varices. SS measurements are better than LS measurements for prediction of high grade varices.

LPH-23

Role of noninvasive markers in predicting esophageal varices in alcoholic cirrhosis

C Vijai Shankar , P Ratnakar Kini, Kani Shaikh Muhammed, K Prem Kumar, T Pugazhendhi, Mohammed Ali

Department of Medical Gastroenterology, Madras Medical College, Chennai 600 003, India

Background: Noninvasive predictors of varices in cirrhosis would reduce the need for screening endoscopies.

Aim: Aim of this study is to assess the role of noninvasive markers like platelet count-spleen diameter ratio, APRI (AST/platelet ratio index), AST/ALT ratio, Lok score, FIB4 score to predict esophageal varices in alcoholic cirrhosis.

Method: Forty-eight patients with alcoholic cirrhosis who came for index screening of varices were prospectively evaluated for noninvasive markers using laboratory tests like platelet count, AST, ALT, INR, USG abdomen and were subjected for endoscopy for evaluation of varices. The diagnostic performances of the noninvasive markers were assessed using sensitivity, specificity, positive predictive value and negative predictive value.

Results: Forty-eight patients with alcoholic cirrhosis with mean age of 46 years were included for the study. Majority belonged to Child C (22 patients, 46 %) followed by Child B (14 patients, 29 %) and Child A (12 patients, 25 %). AST/ALT ratio and FIB4 score have better sensitivity and positive predictive value for prediction of varices (80 % and 84 % and 80 % and 4 % respectively) than APRI, Lok score and platelet count-spleen diameter ratio (60 % and 85 %; 60 % and 80 %; 70 % and 82 %). Compared to their role in hepatitis C the noninvasive markers are less specific (specificity in range of 25 % and low negative predictive value around 12 %) in alcoholic cirrhosis for predicting varices except for Lok score in predicting large varices (50 % specificity).

Conclusion: Noninvasive markers though sensitive are less specific in predicting esophageal varices in alcoholic cirrhosis.

LPH-24

Pentoxifylline therapy for hepatopulmonary syndrome: Longer duration is superior to combination with rifaximin, a RCT

Naveen Kumar , K N Chandan Kumar, Sachin Kumar, S K Sarin

Institute of Liver and Biliary Sciences, D-1, Vasant Kunj Marg, New Delhi 110 070, India

Aims: Hepatopulmonary syndrome (HPS) occurs in around 10 % cirrhotic patients. TNF alpha and nitric oxide mediated vascular dilatation constitutes pathogenetic mechanism. Treatment remains unsatisfactory with variable duration pentoxifylline therapy and limited other options. Antibiotic therapy needs proper evaluation.

Methods: A RCT of pentoxifylline and rifaximin combination (Gr A) for 12 weeks who initially failed 12 weeks pentoxifylline monotherapy and was compared with long-term pentoxifylline monotherapy (Gr B). HPS patients with intrapulmonary vascular dilation on saline contrast ECHO and baseline PaO2 <90 mmHg were included in study. Patients with significant cardiopulmonary illness, advanced encephalopathy, antibiotic use, listed for transplant or malignancy were excluded. The primary end-point was oxygen saturation improvement at least 5 mmHg from baseline.

Results: Forty-two patients were enrolled. Most patients were male (93 %), mean age 49 yrs with etiology of cirrhosis predominantly ethanol or cryptogenic (43 % and 45 % respectively). The mean baseline parameters were CTP-8.6, MELD-15.6±2.7 and PaO2-71± 8 mmHg. No correlation between shunting grade and HPS severity was found. The response rate of 19 evaluable patients in two arm (9 in Gr A and 10 in Gr B) was 67 % and 60 % respectively after treatment of 24 weeks. Twelve and 24 weeks pentoxifylline treatment response was 27 % vs. 63 %. Associated improvement in maximal oxygen uptake (VO2 max) was seen in responders.

Conclusions: Pentoxifylline therapy is beneficial in HPS with the response seemingly related to the treatment duration. There is no additional benefit of adding rifaximin to pentoxifylline. Improvement in cardiopulmonary profile occurs in responders.

LPH-25

Predictors of terlipressin related adverse effects in liver cirrhosis and its influence on survival

Ashok Choudhury , Chandan Kumar Kedarisetty, Awinash Sinha, Chetan Kalal, Pawan Wagle, Chitranshu Vashistha, Rakhi Maiwall, Ajeet Bhadoria, S K Sarin

Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj Marg, New Delhi 110 070, India

Background and Aims: Terlipressin is widely used for control of acute variceal bleed (AVB) and hepatorenal syndrome (HRS) with a survival benefit. The aim of study is to identify the degree and severity of adverse events (AE) and their predictors on use of terlipressin.

Methods: Adverse events among consecutive patients with cirrhosis admitted and who received intravenous terlipressin were analyzed retrospectively. Dose of terlipressin used as per institute protocol.

Results: Total 332 patients, 294 (89 %) male. Predominant etiology was ethanol (n=147, 47.3 %), cryptogenic (n=73, 22 %), HBV (n=37, 11 %), HCV (n=32, 9.6 %) and NASH (n=27, 8 %). Median CTP 11 (range 9-12), MELD 24 (range 17-32) and MELD Na 28 (range 21-34). Terlipressin was used in AVB (52 %) and HRS (48 %). AE were noted in 25 (7.5 %) cases. Occurrence of AE did not differ with etiology. AE were significantly seen when used for AKI (OR-2.7, 95 % CI=1.134-6.462, p<0.025). AE were lactic acidosis (28 %), cyanosis (28 %), cardiac ischemia (8 %), bowel ischemia (8 %) and loose stools (16 %). Total in-hospital mortality was 34.9 % (n-116) and associated with AE (OR:5.19). Lactic acidosis had highest mortality (85.8%). Predictors of AE were bilirubin ≥6 mg/dL (OR-3.08, 95 % CI 1.017-9.382, p<0.05), creatinine ≥3.5 mg/dL (OR-3.65, 95 % CI 1.097-12.614, p<0.05) and nonsignificant correlation with age ≥70 years and Hb <5 gm %. On multivariate analysis, bilirubin ≥6 mg/dL, Na ≤135 meq/dL, CTP ≥10 and MELD ≥25 were significantly associated with poor survival while on terlipressin with AE.

Conclusion: Terlipressin should be used cautiously in HRS with bilirubin ≥6 mg/dL, creatinine ≥3.5 mg/dL, MELD ≥25 and CTP ≥10.

LPH-26

WITHDRAWN

LPH-27

Budd-Chiari syndrome: Experience of therapeutic radiological intervention

Mohd Talha Noor, Kailash Patel, Abhishek Kathuria , Bhagwan Singh Thakur

Departments of Gastroenterology and Radiology, Sri Aurobindo Institute of Medical Sciences, Indore 543 111, India

Introduction: Budd-Chiari syndrome (BCS) is a treatable cause of chronic liver disease. In this study, we evaluated the role of therapeutic radiological intervention in the treatment of BCS.

Methods: Nine consecutive cases of BCS were recruited at a tertiary care hospital. Evaluation of these patients included hemogram, biochemical tests, ultrasonography abdomen with color Doppler, contrast-enhanced computed tomography of abdomen and digital subtraction angiography. All patients depending on pattern of inferior venacava (IVC) and/or hepatic vein (HV) obstruction were triaged for radiological intervention in addition to anticoagulation therapy.

Results: There were 6 females and 3 males with a mean age of 26.2±5.2 years. The most common symptom was abdominal distension in nine patients (100 %) followed by abdominal pain in seven (77.7 %), upper gastrointestinal bleed in four (44.4 %) and jaundice in three patients (33.3 %). The most common clinical finding was ascites in nine patients (100 %), hepatomegaly in eight (88.8 %), splenomegaly in four (44.4 %). Ultrasound Doppler showed HV thrombosis in all 9 patients (100 %) and IVC thrombosis in six (66.6 %) patients. Radiological intervention was successful in 8 patients :direct intrahepatic portosystemic shunt (DIPS) in three (33.3 %), HV plasty in two (22.2 %), HV plasty with IVC plasty in one (11.1 %), HV stenting+IVC stenting in one (11.1 %), IVC plasty+stenting in one (11.1 %) and one patient was advised medical management only as radiological intervention was unsuccessful. All patients were given oral anticoagulants. Response to therapy was good in all patients. Procedure was uncomplicated in all patients except one who developed pulmonary thromboembolism which was managed by local thrombolytic therapy.

Conclusion: BCS is an important treatable cause of chronic liver disease. The role of radiological intervention is promising.

LPH-28

WITHDRAWN

LPH-29

Incidence of minimal hepatic encephalopathy in decompensated chronic liver disease patients using psychometric hepatic encephalopathy score

B Sajeeth Manikanda Prabu , K Muthukumaran, G Ramkumar, R Balamurali, T Rajkumar Solomon, A Murali, P Ganesh

Kilpauk Medical College, Chennai 600 010, India

Aim: To detect the incidence of minimal hepatic encephalopathy in decompensated chronic liver disease (DCLD) patients using psychometric HE score.

Materials and Methods: Fifty decompensated cirrhotic patients who did not have features of encephalopathy clinically were included in the study. All underwent psychometric HE scoring and was correlated with CTP score.

Results: Out of 50 patients, 33 (66 %) did not complete scoring system within the stipulated time. The etiology of cirrhosis was ethanol in 42 patients (84 %) and hepatitis B in 8 patients (16 %). Among those 33 patients who had evidence of minimal hepatic encephalopathy, 12 patients (36.36 %) belonged to Child-Pugh Class C, 18 patients (54.54 %) and 3 patients (9 %) belonged to Child-Pugh Class B and A respectively.

Conclusion: The incidence of minimal hepatic encephalopathy was 66 % in our study. Minimal hepatic encephalopathy was seen more in patients with Child Class C and B.

LPH-30

Effect of lactulose administration on gut microbiota in patients with liver cirrhosis

Rakesh Aggarwal, Amit Goel, Aditya N Sarangi, Ankur Singh, S Avani

Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Objective: Beneficial effect of lactulose on hepatic encephalopathy (HE) is believed to be mediated, at least partially, by changes in gut flora. We therefore compared bacterial flora in the gut lumen before and after lactulose administration using next-generation sequencing.

Methods: Patients with liver cirrhosis without HE, who did not have gastrointestinal symptoms, or current or recent (6 weeks) intake of lactulose or drugs that alter gut motility or flora were recruited, irrespective of etiology or severity of cirrhosis and minimal HE. Morning stool specimens collected at baseline and after ≥6 weeks of lactulose were processed for DNA extraction, amplification of V3 region of bacterial 16S rRNA, and next-generation sequencing of the DNA library so generated. From sequencing data, operational taxonomic units (OTUs) were assigned by comparison with Greengenes database. For OTUs accounting for ≥0.005 % of total sequences in either group, abundances were compared using paired t-test.

Results: Twenty-two specimens from 11 patients (median age: 51 [range 30-64] years, 6 male) yielded a mean of 622,748±266,087 high-quality reads (total: 13,700,461 reads), which were assigned to 17,716 OTUs. Abundances of various top phyla were similar before and after 48 (41-90) days of lactulose [Bacteroidetes (72.2±12.1 % vs. 62.8±23.3), Firmicutes (20.1±11.0 % vs. 23.8±20.2), Proteobacteria (5.7±6.1 % vs. 9.5±7.2), Actinobacteria (0.6±1.1 % vs. 1.8±3.4) and Fusobacteria (0.6±0.2 % vs. 1.7±5.6)]. No bacterial class, order, family, genus or species showed a significant change in abundance after lactulose.

Conclusion: Six-week lactulose administration in patients with cirrhosis did not lead to any discernible change in fecal bacterial flora.

LPH-31

Predictors of short-term mortality in patients with cirrhosis and spontaneous bacterial peritonitis

A B Suthanu , K S Prasanth, Tony Joseph, George Peter Paul Cheruvathoor, P V Mashhood, Yamuna R Pillai, K R V Kumar, N Premaletha, S Srijaya

Department of Medical Gastroenterology, Medical College, Thiruvananthapuram 695 011, India

Background/Aims: Spontaneous bacterial peritonitis is the most common infection in patients with decompensated cirrhosis. The short-term mortality of SBP is high even with standard treatment. However, the factors that affect the short-term mortality in patients with SBP need to be further clarified. The aim of this study was to investigate the predictors of 30 day mortality in patients admitted with cirrhosis and spontaneous bacterial peritonitis.

Methods: We retrospectively collected the data of 98 cirrhosis patients diagnosed with SBP. All patients with diagnosis of SBP were given the standard medical treatment. Clinical parameters and laboratory investigations collected and analyzed. Multivariate regression modeling and receiver operating characteristic (ROC) curves were utilized for statistical analysis.

Results: Out of the 98 patients 72 % were men and 30 day mortality was 23.5 % (24). On univariate analysis low serum sodium (<132) (odds ratio (OR) 4.73; 95 % confidence interval CI: 1.47 - 15.20 p=.006), MELD (>20) (OR 5.88; CI 2.07 - 16.66, p<0.001) presence of encephalopathy (OR 7.42, CI 2.65-20.75, p<0.001) and resistant SBP (OR 2.74 CI 1.06 - 7.05, p=.033) were all statistically significant factors predicting the mortality. On multivariate analysis MELD, encephalopathy and sodium were independent predictors of 30-day mortality. A MELD score of >20 was associated with a sensitivity of 75 %, a specificity of 66.2 %. A Na level of <132 was associated with a sensitivity of 83.3 %, a specificity of 48.6 %. Presence of encephalopathy has a sensitivity of 70.8 % and specificity of 75.3 in predicting mortality.

Conclusions: MELD >20, sodium <132 and encephalopathy were associated with higher mortality rates in cirrhotic patients with SBP.

LPH-32

Comparative evaluation of ultrasound, MRCP/MR splenoportovenography and endoscopic ultrasound in diagnosis of portal cavernoma cholangiopathy

Gyan Prakash Rai , Sandeep Nijhawan

Department of Gastroenterology, Sawai Man Singh Medical College, J L N Marg, Jaipur 302 004, India

Background: MRCP with MR splenoportovenography (MRSPV) is modality of choice for map** of the biliary and vascular abnormalities in PCC. EUS is also useful in delineating the cause of biliary obstruction and delineating the type of choledochal collaterals.

Patients and Method: From January to July 2014 we evaluate 36 diagnosed patients of EHPVO with US, MRCP with MRSPV and Linear EUS.

Result: Mean age of patients was 23 yr (14-38 yrs), 26 patients were male (78 %) and 10 patients were female. Biliary changes were seen in 31 patients (88 %) while symptoms were seen in only 7 patients (18 %). Biliary changes seen in extrahepatic ducts in 100 % of patients while intrahepatic ductal changes seen in only 14 patients (40 %). Sensitivity of EUS is approximately 100 %, equal to MRCP with MRSPV (gold standard of dx). Epicholedochal collaterals better demonstrated with MRI as dot like enhancing lesion on CBD but MRI and EUS was seen as equally sensitive in delineating the paracholedochal collaterals. Intracholedochal collaterals and perforators was better seen with EUS. We have not seen any subepithelial collaterals.

Conclusion: EUS appears to be the investigation of choice for tracing the origin, caliber, entry and course of collaterals outside and through the CBD in PCC. EUS can also differentiate between intracholedochal collaterals, CBD stone, stricture and mass. Layer-wise localization of varices is best done by color Doppler EUS and is important because subepithelial and intracholedochal varices can cause hemobilia during ballon dilatation and stenting of CBD.

Liver – Viral Hepatitis

LVH-01

Factors influencing response of chronic hepatitis C to peginterferon and ribavirin therapy

T Agarwala , G Ray

B R Singh Hospital, Sealdah, Kolkata 700 014, India

Background: Though peginterferon and ribavirin remains the SOC in patients of chronic hepatitis C in India, the scenario might change with introduction of oral drugs. So better delineation of factors influencing outcome of such treatment is needed for optimal drug use.

Methods: Fifty eligible patients of chronic hepatitis C (anti-HCV and HCV RNA positive >6 months) attending the liver clinic from June 2007 to June 2013 underwent therapy with peginterferon and ribavirin for standard duration in standard dosage according to genotype and body weight. All patients were CTP class A, 13 had compensated cirrhosis based on biochemical, radiological, endoscopic and/or histological investigations. Patient with decompensation were excluded. Factors (affecting SVR) studied were age, sex, BMI, presence of diabetes mellitus (DM), alcohol use, viral load and genotype, presence of cirrhosis or risk factors for acquiring HCV and IL28B.

Results: Mean age 48.5+14.64 (range 7-78) years, 27 males, median viral load 84,500 (range 3000 - 4 x 109) vcopies/mL, DM 17, risk factors 21, alcohol intake 7 patients. Overall EVR 46 (92 %), EOTR 43 (86 %), SVR 32 (64 %). Genotypes (SVR %): G1=9 (6, 66.7 %) G2=1 (1, 100) G3=37 (24, 64.9 %) G4=2 (1, 50 %) G6=1 (0), IL28B CC 17/20, TT 3/20. Significant predictors of SVR on univariate analysis were age, cirrhosis, absence of DM, EVR and EOTR but on multivariate analysis they were (with odds ratio and confidence interval) age 1.13 (1.02 - 1.25), cirrhosis -0.09[0.01-0.7), absence of DM 11.5 (1.09-121.44).

Conclusions: SOC for hepatitis C showed moderate overall response with definite predictors.

LVH-02

Hepatitis C infection and Lichen planus variants: A study of 6 cases

Ivy Sandhu , Harneet Singh

Kasturba Medical College, Manipal 576 104, India

Chronic hepatitis C infection is associated with extrahepatic manifestations in up to 35 % patients and these are most commonly rheumatological (19 %) or cutaneous (17 %). An important cutaneous association with chronic hepatitis C infection is Lichen planus. Herein are reported 6 patients with chronic hepatitis C infection who presented with skin lesions of different variants of Lichen planus, proven by skin biopsy. Hepatitis C infection was diagnosed by ELISA in all the patients. Out of the 6 patients, 2 were diagnosed to be having Lichen planus pigmentosus, 2 had hypertrophic Lichen planus and 1 each had eruptive Lichen planus and segmental Lichen planus. Although many studies have reported association of hepatitis C with classical and oral Lichen planus but we report these patients because they presented with other rarer variants of Lichen planus.

LVH-03

Determining modes of transmission of hepatitis C virus

Mrudul Dharod , Deepak Amarapurkar

Department of Gastroenterology and Hepatology, Bombay Hospital and Medical Research Centre, 12, Marine Lines, Mumbai 400 020, India

Background and Aim: With the availability of new highly effective drugs against hepatitis C virus (HCV), treatment goals of HCV seem achievable, yet complete prevention of HCV transmission is still a distant objective. This study was planned to determine the significance of various factors in HCV transmission.

Methods: Two hundred patients with HCV and 500 blood donors were subjected to interview regarding risk factors pertaining to high risk of HCV transmission such as blood transmission, dialysis, circumcision, tattooing, body piercing, shaving habit, surgery and multiple injections.

Results: HCV patients (mean age: 49.2±13.74 years) were significantly older as compared to blood donors (35.13±9.80). Forty-four percent of HCV individuals were females, as against 20.80 % of blood donors. None of our patients had a history of injection drug abuse. On regression analysis, history of blood transfusion (p<0.001, OR 96.16), especially prior to 2002 (p=0.005), dialysis (p<0.001, OR 36.19), circumcision (p<0.001, OR 11.75), shaving in a barber shop (0.002, OR 3.34), body piercing (0.002. OR 4.40) and a history of multiple injections (<0.001, OR 5.98) were the factors found significantly associated with HCV population. Tattooing (p=0.071, OR 0.10) and dental treatment (p= 0.006, OR 0.20) were more prevalent in blood donors and had a negative correlation with HCV transmission. Average number of injections received for common medical ailments per patient/year was 5.53±4.75 in HCV group as against 0.74±2.48 in blood donors. Amongst 75 HCV patients, who did not receive any blood transfusion in the past, around 30 % had at least one risk factor of the above, while around a fifth each had 2, 3 and 4 risk factors.

Conclusion: With advances in blood transfusion practices and decrease in HCV transmission via this route, other percutaneous routes including unsafe injection practices play a significant risk in HCV transmission.

LVH-04

Association of host IL28B single nucleotide polymorphisms in viral clearance in hepatitis C virus infected individuals from Eastern India

Alok Chandra, Rushna Firdaus , Aritra Biswas, Anirban Mukherjee, Kallol Saha, Sujit Chaudhuri, Asokananda Konar, Provash Chandra Sadhukhan

Command Hospital, Alipore Road, Kolkata, ICMR Virus Unit, Kolkata, AMRI Hospitals, Salt Lake City, Kolkata, Peerless Hospital and B K Roy Research Centre, Kolkata, India

Background: Genome wide association studies have confirmed that SNPs at rs 12979860 C/T and rs 8099917 T/G are strongly associated in the rate of sustained virological response (SVR).

Objectives: a) To determine the prevalent viral genotypes within hepatitis C virus (HCV) infected groups from Eastern India. b) To determine the impact of SNPs at rs1297960 and rs8099917 in host on outcome of HCV infection.

Method: Two hundred HCV positive patients from Eastern India were assessed for and viral genotypic analysis. Seventy patients were administered Peg-IFN/ribavirin therapy for 24/48 weeks. Viral genoty** was performed using nested RT-PCR followed by direct sequencing methods. Host interleukin 28B genoty** was performed using real-time PCR based single nucleotide polymorphism analysis.

Results: Of 200 seropositive individuals, 73.25 % were found to be RNA positive. HCV genotype 3 (65.87 %) was found in majority followed by genotype 1 (32.08 %). The frequency of CC genotype in host at rs1297960 was 53.94 % compared to CT at 34.84 %. Genotype TT at allele rs 12979860 was 6.0 %. Genotype TT at rs 8099917 was present in 77.5 %, TG in 15 % and GG in 7.5 % individuals. Seventy patients received IFN treatment. CC genotype at rs1297960 was associated with HCV clearance in 84.24 % and CT in 12.85 %. TT at allele rs 12979860 showed HCV clearance in only 2.85 %.

Conclusion: CC, TT the two favorable markers at SNPs rs12979860 and rs8099917. They are strongly associated with viral clearance in HCV infected populations. This information will aid clinicians to effectively design response based treatment regimen.

LVH-05

Effect of vitamin D level on the immunogenicity of hepatitis B vaccination in CKD-ESRD patients on dialysis

Sandeep Nijhawan , Shailendra K Jain, Rajesh Jhrawat, Amit Mathur, Gaurav Gupta

Department of Gastroenterology, Sawai Man Singh Medical College, J L N Marg, Jaipur 302 004, India

Aim: To assess the response of hepatitis B vaccination in ESRD patients and the effect of vitamin D level on the immunogenicity to hepatitis B vaccination.

Method: It was an observational study which includes 30 patients of ESRD on maintenance dialysis, mostly on HD. Patients with anti-HBs antibody positive at baseline were excluded. All were received intramuscular recombinant hepatitis B vaccination at 0, 1, 2 and 6 month 20 μg on each deltoid bilateral. Anti-HBs antibody titers were measure at 4 month of vaccination. The titer >10 mIU/mL was considered as positive. Vitamin D levels were measure at baseline before starting vaccination.

Results: Total 30 patients included were on maintenance dialysis, 80 % on hemodialysis. Mean vitamin D level was 15.023±7.797 ngm/mL. Vitamin D level <10 and <20 were 23.33 % and 83.33 % respectively. At 4 month, overall 19 patients responded to the immunization (63.33 %) and 11 patients were non-responders (36.67 %). At 7 month (one month after completion of vaccination) 61.91 % were responders and 38.09 % were nonresponders. Difference of vitamin D level in responders and non-responders was statistically not significant (p=0.106). In responder titer >100 mIU/mL was in 42.86 % at 7 month. Good responders (titer >100mIU/mL) have higher vitamin D level than weak responders (21.516±10.802 ngm/mL vs. 10.097±3.657 ngm/mL, p=0.369). The association of vitamin D level and anti-HBs antibody titer were not significant (r=0.034 and 95 % CI was -0.427 to 0.481, p=0.891) in those who were responders.

Conclusion: Most patients on dialysis are vitamin D deficient. Vitamin D level was lower in nonresponders and weak responders as compared to responders and good responders however it did not significantly affect response to hepatitis B vaccination in dialysis patients.

LVH-06

Prevalence of hepatitis E virus infection during pregnancy

Swati Singh , Premashis Kar

Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, Bahadur Shah Zafar Marg, Delhi Gate, Delhi 110 002, India

Background: Hepatitis E virus (HEV) infection in pregnant women is more common and fatal during the third trimester. The incidence of HEV infection in pregnancy is high and a significant proportion of pregnant women can progress to fulminant hepatitis.

Objective: To determine the prevalence of hepatitis E virus infection during pregnancy.

Method: The study included consecutive 130 pregnant patients with jaundice during January 2011 to December 2013. Serological evaluation of all virological markers like HEV IgM, HAV, HBsAg and anti-HCV was done by using ELISA. HEV viral load was estimated by real time PCR using standard HEV viral load estimation kit.

Result: The prevalence of hepatitis E virus infection during pregnancy has been found to be 49.23 % (64/130). The mean maternal age, gestational age at delivery of the HEV infected pregnant patients were 24.32+4.25 years, and 33.41+3.94 weeks. Occurrence of hepatitis A virus infection and hepatitis C virus infection during pregnancy were 11.53 % (15/130) and 4.61 % (6/130). Only 5.38 % cases were presented with co-viral infection. The total leukocytes count (TLC), serum bilirubin, AST, ALT, ALP levels and prothrombin time were significantly higher in cases as compared to control cases. In the ALF pregnant cases, maternal mortality accounts for 15 % (10/64). HEV viral load in ALF pregnant women was 139994.0±103104.17 copies/mL as compared to AVH pregnant women 768.92±1105.40 copies/mL (p<0.05).

Conclusion: Hepatitis E virus infection is the most common form of hepatitis in pregnant women.

LVH-07

Association of hepatitis B virus precore and basal core promoter mutations in fulminant viral hepatitis

Neha Gupta , J K Choudhary, M K Tripathi, A Ranjan, V K Dixit, A K Jain

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India

Background: Infection with hepatitis B virus (HBV) is associated with wide manifestations, ranging from acute self-limited infection to fulminant hepatitis, chronic hepatitis with or without cirrhosis and liver failure to hepatocellular carcinoma. Patients with acute viral hepatitis (AVH) and mutations in HBV precore (PC) and basal core promoter (BCP) sometimes develops fulminant hepatitis B (FHB). The survival rate of FHB patients is still low and they require careful management including liver transplantation.

Aim: To evaluate association of PC and BCP mutations in HBV infected FHB subjects.

Patients and Methods: Total 78 (64 AVH and 14 FHB) subjects were enrolled in this study. The determination and confirmation of precore and basal core promoter sequence and mutation of HBV was done by using PCR followed by RFLP with restriction enzyme RsaI and Sau3AI and sequencing.

Results: Frequency of hepatitis B e antigen (HBeAg) negative and HBeAg positive in AVH subjects were 40 (62.5 %) and 24 (37.5 %) and in FHB subjects were 11 (78.6 %) and 3 (21.4 %) respectively. The prevalence of mutation in HBeAg negative AVH subjects was PC 3 (7.5 %), BCP 6 (15 %) and PC+BCP 8 (20 %) where as in HBeAg negative FHB subjects was PC 5 (45.4 %), BCP 1 (9.1 %) and PC+BCP 3 (27.3 %). Biochemical profile like serum bilirubin (23.94±7.59 mg/dL), ALT (558.11±416.89 IU/L), serum albumin (2.93±0.35 mg/dL), prothrombin time (3.38±1.10 INR) and HBV DNA (4.66±0.40 log10 copies/mL) was noted in PC/BCP mutated HBeAg negative FHB subjects.

Conclusion: PC/BCP mutations were noted two fold higher in HBeAg negative FHB subjects in comparison to AVH subjects, these mutations may play important role in the development of FHB.

LVH-08

Diabetes mellitus is more commonly associated with IL28b non-C/C genotype than in C/C genotype in patients with hepatitis C virus

Varun Gupta , Ashish Kumar, Praveen Sharma, Pankaj Tyagi, Naresh Bansal, Vikas Singla, Anil Arora

Sir Ganga Ram Hospital, Old Rajender Nagar, Delhi 110 060, India

Background: IL28b polymorphism is an important predictor for hepatitis C virus (HCV) response to therapy; and IL28b C/C genotype is considered to have favorable response as compared to non-C/C genotype. However, whether IL28b genotypes also influence other non-treatment related clinical parameters is not clear.

Methods: In this retrospective analysis, patients with HCV related chronic liver disease attending Sir Ganga Ram Hospital, New Delhi, from 2012 to 2014 were analyzed. The SNPs rs12979860 (IL28B) was investigated by RT-PCR and IL28b genotypes were correlated with various clinical parameters.

Results: A total of 115 patients were included in the study (median age 48, range 15-76 years; 70 % males). The most common IL28b genotype was C/C 53 % (61/115), while rest 47 % were non-C/C [C/T 42 % (48/115) and T/T 5 % (6/115)]. Overall, 43/115 (37 %) patients had chronic hepatitis, while rest 72/115 (63 %) were cirrhotics. The IL28b genotype distribution was similar in chronic hepatitis and cirrhotic groups. Clinical and laboratory parameters like Hb, WBC, platelets, bilirubin, AST, ALT, and albumin were similar in C/C and non-C/C genotypes. Diabetes mellitus was found in 22 % (25/115) of patients. Patients with non-C/C genotype had significantly higher prevalence of diabetes mellitus than patients with genotype (31 % [17/54] vs. 13 % [8/61]; p=0.023).

Conclusion: Diabetes mellitus was found to be more commonly associated with IL28b non-C/C genotype than in C/C genotype in patients with HCV. Since insulin resistance is more common in carriers of the T allele of SNP rs12979860 than in CC homozygotes, this may explain higher prevalence of diabetes in non-C/C genotypes.

LVH-09

iNOS and eNOS genotypes and expression in hepatitis E-related acute liver failure

Rajib Kishore Hazam , Jayanta Borkakoti, Premashis Kar

Department of Medicine, Maulana Azad Medical College, Bahadur Shah Zafar Marg, Delhi Gate, Delhi 110 002, India

Purpose: The study was aimed to determine the role of iNOS and eNOS genotypes and their expression in hepatitis E virus (HEV)-related acute liver failure (ALF).

Methods: The study group included 294 acute viral hepatitis (AVH), 82 ALF and 331 healthy controls. Expression study of iNOS and eNOS was done using commercially available ELISA kits. Polymorphism of iNOS C150T and eNOS G894T was studied using the PCR-RFLP method.

Results: On comparing the iNOS levels corresponding to its genotype in the study group, we observed that the subjects carrying the CT+TT mutant genotype had significantly higher levels of iNOS compared to the wild type CC genotype (24.9±6.9 vs.16.74±5.1; p<0.001, 62.16±1.6 vs. 54.26 ±6.1, p<0.001, and 10.57±5.15 vs. 7.36±2.5, p<0.001). Similarly, on comparing the eNOS levels corresponding to its genotype in the study groups, we observed that the subjects carrying the GT+TT mutant genotype had significantly higher levels of eNOS compared to the wild type GG genotype (27.3±7.2 vs.21.45±5.1, p<0.001, 64.1±1.8 vs. 58.5 ±2.8, p<0.001 and 17.9±4.8 vs.14.6±4.3, p<0.001). Significant positive correlation was observed between the iNOS and eNOS levels in the HEV-infected patient (AVH and ALF) and the severity of disease parameters i.e viral load, prothrombin time, total bilirubin, direct bilirubin, SGOT, and SGPT levels.

Conclusion: iNOS and eNOS mutant genotype significantly increases the levels of iNOS and eNOS, as compared to wild type. The iNOS C150T polymorphism and the eNOS G894T polymorphism and high levels of iNOS and eNOS are associated with an increased risk of HEV-related acute hepatitis and liver failure.

LVH-10

Expression of IP-10 and RANTES in peripheral blood of hepatitis B infected patients and their comparative analysis

Arttrika Ranjan , M Srivastava, J K Choudhary, M K Tripathi, N Gupta, S K Shukla, V K Dixit, A K Jain

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India

Background and Aim: Chronic infection related to hepatitis B virus infection is a serious problem worldwide. Persistent HBV infection in which HBV is not completely eradicated from hepatocytes and peripheral blood is the main feature of chronic hepatitis B (CHB). The reason for which is weak immune response. Chemokines plays an important role in immune response. This study focuses on the expression of two chemokines RANTES and IP-10 in peripheral blood.

Method: Blood samples from 120 CHB patients were collected in EDTA vials. RNA was isolated from peripheral blood using Trizol reagent. Quantitative real time PCR was performed for chemokines RANTES and IP-10.

Results: The results revealed that the expression of both these chemokines was up-regulated in HBeAg positive subjects. Increased expression i.e. nearly 17 folds was observed in HBeAg negative subjects for RANTES while IP-10 was around 6 folds down regulated. One of the important finding was that expression of IP-10 was lower in HBeAg negative subjects as compared to HBeAg positives. Fold change in case of IP-10 and RANTES in CHB was found to be significantly correlated (p<0.05).

Conclusion: Therefore it can be concluded that both these chemokines help in recruitment of immune cells at the site of inflammation. Conclusion with respect to clinical diagnostics suggests biopsy for HBeAg negative subjects as to assess the early progression of the disease.

LVH-11

Frequency of hepatitis D virus infection among persons with hepatitis B virus infection in northern India: A molecular study

Shankar Lal Jat , Neha Gupta, Tarun Kumar, Amit Goel, Vishwajeet Yadav, Rakesh Aggarwal

Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Background: Prevalence of hepatitis D virus (HDV) infection among persons with hepatitis B virus (HBV) infection varies around the world and appears to have declined in recent years. Studies from India, mostly during the 1990s, showed anti-HDV seroprevalence rates of 1 % to 50 %. Since there are no molecular data on HDV prevalence from India, we studied the prevalence of HDV infection rates in a group of HBV-infected patients in northern India.

Methods: During 2012-13, sera were collected from 169 patients with HBV infection, irrespective of clinical presentation or severity. Their sera were tested for HDV RNA using a sensitive real-time reverse transcription-PCR assay and for IgG anti-HDV antibodies (HDV-IgG; DSI, Gallarate, Italy).

Results: Of the 169 subjects (133 [79 %] male; median age 33 [range 18-74] years), 103 (61 %; 30 [18-60] years; 76 male) had chronic hepatitis, 38 (23 %; 45 [22-67] years; 34 male) had cirrhosis, 27 (16 %; 33 [18-74] years, 23 male) had acute viral hepatitis, and 1 (0.6 %; 18 years]; female) had acute liver failure. Of the 169 sera, all were negative for IgG anti-HDV antibody and HDV RNA.

Conclusion: HDV infection is infrequent among persons with HBV infection in northern India.

LVH-12

WITHDRAWN

LVH-13

Aspartate aminotransferase/platelet ratio index and neutrophil lymphocyte ratio to assess fibrosis/cirrhosis in chronic hepatitis B

Tony Joseph , Prasanth Sobhan, Suthanu Bahuleyan, Chethan Govindaraju, Srijaya Sreesh, Premalatha Narayanan, Kattoor Ramakrishnan Vinayakumar

Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram 695 011, India

Background: Because of the invasive nature of liver biopsy, simple and less costly noninvasive tests are needed to assess fibrosis/cirrhosis.

Aim: To compare the efficacy of the aspartate aminotransferase/platelet ratio index (APRI) and neutrophil lymphocyte (N/L) ratio to predict fibrosis/cirrhosis in chronic hepatitis B (CHB).

Methods: This is an observational study based on the five year (2008-2014) data available in our electronic records of patients with CHB who underwent liver biopsy. Patients with hepatitis B flares were excluded. All liver biopsies were grouped into those with significant fibrosis (F2-F4) and cirrhosis (F5-F6) according to Ishak staging and hepatic activity index (HAI) were also recorded (0-18).

Results: Total number of patients were sixty-eight. APRI was high in both groups and showed statistical significance on multivariate analysis. N/L ratio showed positive correlation with HAI according to Spearman’s rank test (r=+0.686, p 0.67 and APR >1.012, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of APRI for cirrhosis was 94.7 %, (95 % CI 75.4-99.1) 93.9 % (95 % CI 83.5-97.9), 85.7 % (95 % CI 65.4-95.0) and 97.8 % (95 % CI 88.9-99.6), respectively with accuracy rate 94.1 % and Kappa value 0.858.

Conclusion: APRI may be useful index in assessing fibrosis and cirrhosis in CHB. N/L ratio cannot be assumed to be good predictor of fibrosis/cirrhosis at this point of time, though it showed positive correlation with HAI.

LVH-14

The mutational analysis in the precore and core region of hepatitis B virus DNA in the patients from Guwahati, Assam

Namrata Kumari 1 , Snigdha Saikia 1,2 , Kangkana Kataki 1 , Prajjal Baruah 1 , Subhash Medhi 1 , Bhavadev Goswami 2 , Premashis Kar 3 , Manab Deka 1

1Department of Biological Science, Gauhati University, Guwahati 14, Assam, 2Department of Gastroenterology, Gauhati Medical College, Guwahati, Assam, and 3Department of Medicine, Maulana Azad Medical College, Bahadur Shah Zafar Marg, Delhi Gate, Delhi 110 002, India

Background and Aim: Mutations in the precore and the core promoter are frequently found in hepatitis B envelope antigen (HBeAg)-negative chronic hepatitis B. The aim of this geographic wide study were to determine the prevalence of HBV precore and core variants and the association between these variants and and severity of liver disease.

Method: A total of 4,403 cases were screened from patients suffering from different types of liver diseases AVH (n=184), FHF (n=2), chronic hepatitis (n=2693), cirrhosis (n=1488), HCC (n=36) with mean age of 41.19±13.24 years with sex ratio of male: female=15:4 for the presence of HBV infection and they were further tested for precore and core promoter variants (G1896A and C1858T and A1762T and G1764A) by using specific PCR primers with related to HBeAg.

Result: Out of 5,480 cases 278 (5 %) were found as HBsAg positive and 117 (42 %) were found as HBV DNA positive as follows AVH (n=48), CAH (n=43), Cirr (n=14) and HCC (n=12). Precore and core promoter variants were found in 25 % and 43 % of patients with HBV infection in the Eastern India population. Precore and core promoter variants were more common in HBeAg-negative (n=76) than in HBeAg-positive patients (n=41) (precore vs. core, 25 % vs. 43 %; respectively, p<0.001). Precore and/or core promoter variants were associated with higher serum HBV DNA levels in HBeAg-negative but not in HBeAg-positive patients.

Conclusion: The hepatitis B e antigen (HBeAg) in serum is known to be an important marker of a high degree of viral infectivity. Our data suggest a high prevalence of precore and core promoter mutation in patients with HBeAg-negative chronic hepatitis B.

LVH-15

A rare case of telbivudine induced myopathy

D Thennarasu , Tarakeshwari, G Ramkumar, N Muthukumaran, R Balamurali, T Rajkumar Solomon, P Ganesh

Introduction: Chronic hepatitis B is a major problem all over the world. The GLOBE trial showed that telbivudine has more potent antiviral activity and less viral resistance compared with lamivudine. A minority of telbivudine-treated patients experienced creatine kinase (CK) elevation, usually transient, and myopathy occurred rarely. We report here a rare case of telbivudine induced myopathy in a patient with chronic hepatitis B.

Case Presentation: We report 50-year-old female diagnosed with chronic liver disease - HBV related who was started on T.Telbuvidine for chronic hepatitis B presented with progressive weakness of both lower legs and upper limbs, difficulty in ascending stairs one month after starting T.Telbuvudine. She developed dysphagia, dysarthria and nasal regurgitation. On examination POWER: U/L: 3/5 L/L: 3-4/5, her neck flexors were weak, trunk muscles were weak and she was walking with support. Her nerve conduction studies were suggestive of myopathy and total CPK was 2,450. T. Prednisolone and T. Tenofovir was started and T.Telbivudine stopped. Patients muscle strength improved dramatically and she was able to walk without support and her total CPK returned to normal.

Conclusion: We report a rare case of telbivudine induced myopathy with serum CPK elevation in CHB patient. Physicians should take into consideration the possibility of such an adverse reaction in their clinical practice and telbuvudine induced myopathy dramatically improves after discontinuation of the drug. Further closer monitoring is recommended for the evaluation of CK elevation or myopathy in patients who were treated with telbivudine.

LVH-16

Does IFN-alpha antibody levels have any clinical significance in treatment of chronic hepatitis C patients?

Premashis Kar 1 , Praveen Bharti 1 , Phani Kumar Gumma 1 , Soumya Jyoti Chowdhury 1 , Vijay Kumar Karra 1 , Bhudev Chandra Das 2

1Department of Medicine, Maulana Azad Medical College, Delhi University, Maulana Bahadur Shah Zafar Marg, Delhi Gate, New Delhi 110 002, India, and 2 Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110 007, India

Background: This study aims to determine the influence of neutralizing IFN-α antibodies (IFN-α-Ab) on oligoadenylate synthetase1 (OAS1) gene expression and hence the viral clearance in the outcome of treatment in chronic hepatitis C (CHC) patients.

Method: Concentrations of serum IFNα-Ab in HCV infected (n=122) and healthy individuals (n=50) were measured using quantitative ELISA. Expression of hepatic OAS1at mRNA level was studied by RT-PCR (2-ΔΔCt method) in liver biopsies of CHC patients.

Results: In CHC, interferon treated patients had higher IFN-α-Ab and OAS1 expression compared with treatment-naïve patients, who had lower IFN-α-Ab and OAS1 expression. In the treated group, patients with IFN-α-Ab levels ≥7.45 ng/mL showed significant reduction in OAS1 expression when compared to patients having <7.45 ng/mL IFN-α-Ab. A ≥4.5 fold rise in OAS1 expression was significantly associated with reduction in HCV viral load when compared within treated and treatment-naïve groups. Treatment responders had less IFN-α-Ab than non-responders. Patients failing to clear HCV RNA had shown IFN-α-Ab ≥7.45 ng/mL and OAS1 expression <4.5 fold rise, indicating IFNα-Abs as having an important role in hindering the therapy.

Conclusion: The serum IFN-α-Ab of >7.4 ng/mL was elucidated as the level that reduced the expression of OAS-1 gene, which in turn affected viral clearance during therapy. Our study points to a strategy of constant monitoring of IFN-α-Ab during therapy along with HCV RNA levels.

LVH-17

Comparison of viral kinetics in chronic hepatitis B treatment between entecavir or tenofovir and a combination of entecavir with tenofovir

Anoop C Haridas

Lakeshore Hospital and Research Centre, Kochi 682 304, India

Background/Aims: The primary aim of antiviral therapy is durable suppression of serum HBV DNA to low or undetectable levels in chronic hepatitis B infection. The preferred first line choices for the treatment are entecavir and tenofovir. The present study was done to compare viral load kinetics when treated with single drug entecavir or tenofovir alone and a combination therapy with both entecavir and tenofovir.

Methods: Retrospective study done from January 2009 to December 2013 in patients newly diagnosed as chronic hepatitis B who were started on treatment with either tenofovir or entecavir or combination therapy with both the drugs. These patients were regularly followed up with viral load estimation with Taqman Cobas RT PCR test.

Results: A total of 51 patients were studied. Out of which 27 patients have taken combination therapy with tenofovir and entecavir and 24 patients have taken either tenofovir or entecavir. The viral load logs were plotted in a scatter diagram and linear regression lines and were plotted. Comparison of the trend lines (In GraphPad) did not show any statistically significant difference (p=0.2406).

Conclusion: There is no statistically significant reduction in HBV viral loads with combination therapy of tenofovir and entecavir over monotherapy.

LVH-18

Expression analysis of TLR2, TLR3, TLR7 and TLR9 in hepatitis B virus mediated chronic liver disease and carcinoma in North East India

Kangkana Kataki 1,2 , Parikhit Borthakur 1 , Namrata Kumari 1 , Subhash Medhi 1 , Sujoy Bose 3 , Anupam Sarma 2 , B B Borthakur 2 , Amal Kataki 2 , Manab Deka 1

1Department of Biological Science, Gauhati University, Guwahati, Assam, 2Dr B Borooah Cancer Institute, Guwahati, Assam, 3Department of Biotechnolgy, Gauhati University, Assam, India

Aim: This study is conducted to determine the mRNA expression profile of TLR2, TLR3, TLR7 and TLR9 in PBMC of chronic HBV and HCC mediated by it and to investigate correlation of viral load with severity of the disease.

Method: One hundred and ten samples were taken for the study which includes chronic hepatitis (CH) N=61, cirrhosis (CIRR) N=17, hepatocellular carcinoma (HCC) N=22 and healthy control N=10. HVB DNA detection and genoty** of the virus were determined by nested and multiplex PCR respectively. HBV DNA quantification was performed by kit in Rotor Gene Real Time PCR. mRNA expression analyses of the targeted TLRs were performed in Rotor Gene Real Time PCR using Beta Actin as internet control.

Result: Highest concentration of HBV DNA was quantified in HBV mediated CH followed by CIRR and then HCC. TLR2 and TLR7 expression was very low in all categories. Higher expression of TLR3 in CH and TLR9 in CH and CIRR in comparison to normal is well depicted in this study. TLR2 expression were statistically significant in HCC and CH (p=0.0462) and cirrhosis and CH with (p=0.0171). TLR9 expression was found statistically significant in HCC and cirrhosis (p=0.0262).

Conclusion: It is found that genotype D is most prevalent in North East population and it reveals that with severity of the disease from CH to HCC the viral load of HBV decreases. Our study shows possibility of HBV interacting with TLR signalling which partially explains immune tolerance being induced by the mechanism of HBV infection.

LVH-19

Prospective study of hepatitis B virus infection and its Genotypes in the North-Eastern India

V K Karra, Premashis Kar

PCR Hepatitis Lab, Department of Medicine, Maulana Azad Medical College, University of Delhi, Bahadur Shah Zafar Marg, Delhi Gate, Delhi 110 002, India

Aim: To study the seroprevalence of HBV infection and genotypes associated with various types of liver disease like acute viral hepatitis, fulminant hepatitis, chronic hepatitis, cirrhosis of liver and hepatocellular cancer, blood donors and health care workers prevalent in North eastern states.

Methods: Serological tests for determining HBV infections and questionnaires were performed from 2013 to 2014 among the general population of seven centres of North eastern states. HBV genotypes were determined by multiplex (TSP-PCR).

Results: Total 9,634 participants were screened, serological screening showed 578 (5.9 %) HBsAg positive cases over a period of one year with mean age of 41.19±13.24 years with sex ratio of male:female=15:4. Out of which 212 (2.2 %) were acute viral hepatitis, 4 (0.04 %) were FHF cases, 167 (1.7 %) were chronic hepatitis cases, 121 (1.2 %) were cirrhosis cases, 47 (0.4 %) were HCC cases, 22 (0.2 %) were blood donors and 5 (0.05 %) were health care workers. Two hundred and twenty-eight (39.4 %) samples were found to be HBV DNA positive and the genotypes were D=214 (93.8 %), C=12 (5.2 %), I=2 (0.8 %) from all the participating centre.

Conclusion: Our results showed that the prevalence of HBV is 578 (5.9 %), HCV 102 (1.0 %), HAV 120 (1.2 %) and HEV 15 (0.1 %) respectively among the North eastern states. HBV infection is one of the leading causes of human mortality and morbidity. Hence, for reducing HBV infections, it is necessary to improve the safety of blood and medical treatment.

LVH-20

Study of immunoproliferative marker Ki-67 and risk for hepatocellular carcinoma in hepatitis B virus inactive carriers

Sangey C Lamtha , K D Bhutia, M K Tripathi, J K Choudhary, S K Jena, S K Shukla, A K Jain, V K Dixit

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, Department of Hepatology, S C B Medical College, Cuttack 753 007, and Department of Microbiology, Golitar, National Highway 31A, Sikkim 737 134, India

Introduction: Hepatitis B virus (HBV) infection remains an important public health problem affecting more than 400 million persons worldwide and is a major cause of morbidity and mortality. India lies in the intermediate prevalence zone for HBV endemicity with an estimated HBsAg carrier rate of 4.7 % that extrapolates to 40 million infected individuals. There has been not much data in the literature on the natural course of chronic hepatitis B virus infection in asymptomatic carriers.

Aim: In the present study we studied the immunoproliferative marker Ki-67 in hepatitis B virus inactive carriers to look for hepatocellular carcinoma risk by using Ki-67 antigen antibody staining.

Method and Material: A total of 50 patients (30 male and 20 female) were included for the study after informed consent. Patients with normal platelet count and prothrombin time with INR were admitted for liver biopsy and discharged after observation for a period of 8 hours. Liver biopsy specimen was subjected for immunoproliferative Ki-67 stain and Metavir score. Standard protocol has been followed for staining. The study was approved by the Ethical Committee of Institute of Medical Sciences, Banaras Hindu University, Varanasi.

Result: Staining percentage for immunoproliferative Ki-67 was much lower and in out of 50 patients, only two patients (4 %) were positive for Ki-67 and showed less than one percent positivity, while rest 48 patients (96 %) were all negative for immunoproliferative Ki-67 staining.

Conclusion: We concluded that the HBV inactive carriers are at very low risk for development of hepatocellular carcinoma.

LVH-21

Expression profile of toll like receptor 3, 4 and 7 in acute hepatitis A cases from Kamrup district of Assam

Priyanka Kashyap 1 , Manab Deka 1 , Sujoy Bose 2 , Sangit Dutta 3 , Darshak Shah 3 , Subhash Medhi 1

1Departments of Biological Science, and 2 Biotechnology, Gauhati University, Guwahati 14, Assam, and 3Department of Medicine, Gauhati Medical College, Bhangagarh, Guwahati 781 032, Assam

Introduction: Toll-like receptors (TLRs) are innate sensors that recognize microbial and endogenous ligands, initiating host defense response.

Aim: To study the expression profile of TLR3, 4 and 7 in hepatitis A related acute viral hepatitis cases from Kamrup district of Assam.

Methodology: Subjects enrolled included acute viral hepatitis cases with prior consent out of which 75 were HAV related cases (male:female=23:7 and age=25±8.01) along with healthy controls N=75 collected from Gauhati Medical College, Guwahati. Expression of TLR3, 4 and 7 was done by Real Time-PCR, using β-actin as internal control.

Result: TLR 3 was most significantly upregulated in the acute HAV cases (fold increase 6.17±3.23) compared to TLR7 (fold increase 5.95±1.04) and TLR4 (fold increase 5.15± 0.96). The correlation between the different HAV case groups : acute HAV vs. HAV with cholestasis (p=0.0009; CI:1.4905 to 5.5895 in case of TLR3 expression; p=0.0783; 95 % CI:-12.2944 to 0.6744 in case of TLR4 expression and p=0.0001; 95 % CI:4.6511 to 7.1289 in case of TLR7 expression); acute HAV vs. FHF (p=0.0001; CI:-37.1539 to -33.0261 in case of TLR3 expression; p=0.0407; 95 % CI: 0.2069 to 9.2931in case of TLR4 expression and p=0.000195 %; CI:5.2348 to 9.6852 in case of TLR7 expression) have been found to be extremely statistically significant.

Conclusion: Our study may indicate that TLR3,4 and TLR7 play an important role in the pathogenesis of the HAV virus as all showed upregulation. TLR3 expression showed a upregulation in the FHF cases thus indicating a role of TLR3 in the progression of the disease severity.

LVH-22

Prevalence of hepatitis B infection markers in patients with inflammatory bowel disease

Amol Prabhakar Patil, Ebby Simon, K G Sajith, Ashish Goel, Anna B Pulimood 1 , Priya Abraham 2

Departments Gatsroenterology, 1Pathology, and 2Clinical Virology, Christian Medical College, Vellore 632 004, India

Aim: To study the prevalence of hepatitis B infection markers in patients with inflammatory bowel disease (IBD) in a tertiary care centre in South India.

Material and Methods: We studied 74 IBD patients who presented or were under the follow up of the Department of Gastroenterology, Christian Medical College, Vellore, India. The basic demographic data, IBD related history, risk factors for hepatitis B transmission, hepatitis B immunization details, markers of hepatitis B infection (HBsAg and anti-HBc) and other related investigations were assessed.

Results: Out of the 74 patients, 39 (52.7 %) had ulcerative colitis, 34 (45.9 %) had Crohn’s disease while 1 had indeterminate colitis. The median age of our patients was 39 (IQR: 26-47.3) years while the median duration of disease was 36 months (IQR:16.5-99.3). Present and/or past HBV infection was found in 10 (13.5 %) patients (ulcerative colitis: HBsAg 2.6 %, anti-HBc 15.8 %; Crohn’s disease HBsAg 2.9 %, anti-HBc 6.1 %). Only 7 (9.5 %) had history of 3 doses of hepatitis B vaccination.

Conclusion: In our study, we found that the prevalence of hepatitis B infection markers in IBD patients was similar to that of the general population in India. While several guidelines recommend hepatitis B vaccination in IBD patients, only 9.5 % of our patients had taken the standard 3 dose vaccination schedule.

LVH-23

Adiponectin receptor (Adipor1) in the patients with chronic hepatitis B from the region of North East India

Morteza Kordafshari 1 , Bhava Dev Goswami 2 , Manab Deka 1

1Department of Biological Science, Gauhati University, Guwahati, Assam 14, Assam and 2Department of Gastroenterology, Gauhati Medical College, Bhangagarh, Guwahati 781 032, Assam

Background and Aim: Adiponectin is an adipose specific glycoprotein hormone well known to play important roles in the regulation of glucose and lipid metabolism and known exerts anti-diabetic, anti-inflammatory and anti-atherosclerotic effects. Adiponectin regulates the lipid and glucose metabolism, increases insulin sensitivity, regulates food intake and bodyweight, and protects against a chronic inflammation. The two different isoforms of adiponectin receptor are AdipoR1 and AdipoR2. This study was to examined the expression levels of adiponectin its receptors (adipoR1) in blood sample of patients with chronic hepatitis B.

Methods: A total of around 250 cases of different liver diseases were included for this study. Which included HBV (n=120), HAV (n=60), HCV (n=10) and ALD (n=60) with a mean age of 35±20 and whose male:female is=22:13. The mRNA expression of adiponectin receptor (adipoRI) were analyzed by fluorescence based real time polymerase chain reaction (RT-PCR) in all the cases.

Results: Out of all liver diseases related cases the adipoRI mRNA expression were found as significantly increased in the patients with chronic hepatitis B (45 %). The expression was found less in HCV as well as ALD cases (HCV vs. ALD, p<0.001).

Conclusion: The serum adiponectin is reduced in patient with HBV. So increased mRNA expression of adipoR1 might be to gain more amount of adiponectin in bood or it’s a inflammatory response to HBVin the body.

LVH-24

IL-28B gene polymorphism in chronic hepatitis C related liver disease patients in North-eastern India

Prajjalendra Barooah 1 , Bhaba Dev Goswami 2 , Priyanka Kashyap 1 , Snigdha Saikia 1 , Manab Deka 1 , Subhash Medhi 1

1Department of Biological Science, Gauhati University, Guwahati, Assam 14, and 2Department of Gastroenterology, Gauhati Medical College, Bhangagarh, Guwahati 781 032, Assam

Background and Aim: Treatment response in HCV patients of different ethnicity are varied suggesting an important role of host genetics. IL28B polymorphism (rs12979860C/T) shows differential distribution between racial groups. The present study is aimed to evaluate genotype of IL28B gene polymorphism in treatment undergone and naive chronic hepatitis C virus patients from North-eastern India.

Method: A total of 46 CHC related liver disease cases with mean age of 46.64±10.70 years and sex ratio of 4:1 (M:F) were included in the study, comprising standard anti-HCV treatment undergone N=21 and Nave patients N=25 of which, chronic hepatitis N=39, cirrhosis N=5, HCC N=2. SNP rs12979860C/T on IL28B gene was genotyped by polymerase chain reaction-direct sequencing method.

Result: The frequency of CC genotype was found to be significantly (75 %) higher compared to CT (25 %) genotypes, respectively in patients from North-eastern India. In patients who had undergone treatment, those with CC genotype attained SVR (81 %) more than with CT (40 %) genotype. Among patients with IL28B, CC genotype those with viral genotype 3 attained better treatment response (SVR=92 %) than genotype 4 (SVR=66 %) and genotype 1 (SVR=0 %) respectively.

Conclusion: Higher occurrence of genotype CC-of SNP, rs12979860C/T of IL28B gene and better response of these patients towards standard anti-HCV therapy from North-eastern India is in concurrence with previously reported data from different populations. The small sample size is a limiting factor in this study, which needs further evaluation of response to anti-HCV therapy and IL28B polymorphism in different ethnic groups present within this population.

LVH-25

Comparison of route and dose of hepatitis B vaccine administration in chronic kidney disease (CKD-ESRD) patients on dialysis

Paras Shah , Rajesh Jhorawat, Sandeep Nijhawan, Amit Mathur, Gaurav Gupta

Departments of Gastroenterology and Nephrology, Sawai Man Singh Medical College, J L N Marg, Jaipur 302 004, India

Aim: To compare rates of seroconversion in three arms- (1) Intramuscluar (IM) 40 μg at 0, 1, 2 and 6 month (20 μg each deltoid) (2) Intradermal (ID) 10 μg weekly injection for 8 weeks (3) Intradermal (ID) 40 μg two injection one monthly interval in chronic kidney disease (CKD) patients.

Methods: Total 45 patients of CKD-dialysis included. Patients divided into three groups. All received recombinant hepatitis B vaccine as above. Anti-HBs antibody titer measured at 1 month and after one month of completion of vaccination.

Results: At one month after immunization, each group received 40 μgm vaccine. Response rate in IM, ID low and ID high dose are 20 %, 28.57 % and 28.57 % respectively. Rate of response in both ID route are compared with standard IM route, however difference was not significant. At one month after completion of vaccination response rate in IM, ID low dose and ID high dose are 54.55 %, 60 % and 58.33 % respectively and total dose of vaccine received are 160 μgm, 80 μgm and 80 μgm respectively. Overall rate of seroconversion are equal in IM and both ID route, but at half the dose used in IM route. Cosmetic side effects are more with high dose ID than low dose ID itching, hyperpigmentation and skin noduler.

Conclusion: Rate of seroconversion is equal in both IM and ID route. Cost required in intradermal route is half that of IM route. Number of injection in high dose ID is quite low compared to low dose ID at same efficacy and cost but more cosmetic side effects.

LVH-26

Increased IL-17 producing TFh (CD4+CXCR5+ CCR6+) cells help in HBV seroconversion through TNF-α ± secretion

Ashish Vyas 1 , Shreya Sharma 1 , Arshi Khanam 1 , Ankit Bhardwaj 2 , Shiv Kumar Sarin, 2 Nirupma Trehanpati

1Departments of Research, and 2Hepatology, Institute of Liver and Biliary Sciences. D-1 Vasant Kunj, New Delhi 110 070, India

The incidence of HBsAg spontaneous seroconversion is only 0.5 %. Host immunity is mainly responsible for clearing the virus spontaneously. Tfollicular helper cells (TFH) are a special subpopulation of T helper cells that regulate B cell maturation and antibodies production through IL-21. On stimulation, TFH cells release pro-inflammatory cytokines, which help viral clearance. We investigated the role of TFH cells in HBV clearance, circulating CD4+ CXCR5+ (TFH) cells and their subsets; TFH1, TFH2 and TFH17 were studied.

Patients and Methods: Patients with spontaneous serocoversion (Gr. A, n=11) were taken within 6 months of HBsAg loss and appearance of anti-HBs >10 IU/mL (seroconversion) with negative HBV DNA. Patients in group B were treatment nave, HBeAg+ve and persistently normal ALT 12 months. Serum HBsAg, anti-HBc (T), anti-HBs, quantitative HBV DNA, AST and ATL levels were determined for each patient in Gr A (n=11) and B (n=20). Phenotypic expression of circulating TFH cells and their subtypes was analyzed by flowcytometry. HBV specific response of TFH cells secreting TNF-α, IL-17A were determined by stimulating PBMC’s with HBV surface pooled peptides (207-339) and HBV core pooled peptides (340-388) of HBV genotype D and PMA/Ionomycin. Data were analyzed using the non-parametric Mann-Whitney U test for comparing two groups.

Results: Seroconversion of HBsAg was observed within 3-5 months of acute infection and patients showed anti-HBs titers in the range of (12 to 1000 mIU/mL). CD4+CXCR5+(TFH) cells were significantly increased in Gr B compared to Gr. A (43.3 % vs. 34.7 %, p=0.01). A compared to B showed significantly increased frequencies of CD4+CXCR5+CCR6+TNFα+ and IL17+cells producing pro-inflammatory cytokines, TNF-α (8.96 % vs. 1.29 %, p=0.02) and IL-17A (15 % vs. 1.37 %, p=0.014).

Conclusions: Significantly increased IL-17A and TNF-alpha production by CD4+CXCR5+CCR6+ TFH-17 cells may play a major role in HBV clearance and HBsAg seroconversion.

LVH-27

Hepatitis B virus genotypes prevalent in Northern India and their significance in chronic liver disease

V B Abhilash , V K Dixit, A K Jain, S K Shukla, Manas Behera

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India

Objective: To determine the distribution of hepatitis B virus (HBV) genotypes in northern India and its relationship with severity of HBV related liver disease and HBV DNA levels.

Methods: Thirty-five randomly selected patients with HBV related compensated liver disease formed Group I. Group II was constituted by 35 consecutive chronic hepatitis B patients who got admitted with evidence of first decompensation of the liver disease. The clinical, biochemical and serological profile and serum HBV DNA levels were quantified (RTPCR). HBV genotypes were determined by PCR-RFLP in thirty patients (fifteen from each group).

Results: Genotype D was the most prevalent HBV genotype in the region with 16 patients (53.3 %) followed by genotype A in 11 patients (36.7 %). Three patients (10 %) had mixed genotypes A and D. The ALT values in patients with genotype D were significantly higher than in those with genotype A (p=0.0355; 95 % CI). There was no statistically significant difference between the genotypes regarding the HBeAg status and severity of liver disease as graded by Child class. The HBV DNA levels in patients with genotype D were significantly higher than those in patients with genotype A.

Conclusion: Genotype D and A were the predominant genotypes detected in this part of the country. Genotype D was associated with higher ALT values and higher serum HBV DNA values, indicating its higher replicating ability when compared with genotype A. Genotype D was found to cause severe liver disease as compared to genotype A. HBV genotypes did not show any relationship with HBeAg status.

LVH-28

Role of complement component C4 in treatment response and disease progression in chronic hepatitis C patients

Soumya J Chowdhury , Vijay K Karra, Rupjyoti Bharali, Premashis Kar

1Department of Medicine, Maulana Azad Medical College, University of Delhi, Bahadur Shah Zafar Marg, Delhi Gate, New Delhi 110 002, India and 2Department of Biotechnology, Gauhati University, Guwahati 781 014, Assam

Background: The basis of hepatitis C virus (HCV) evasion of immune system and its response to treatment is still elusive. There have been studies where the level of C4 has been found to be associated with HCV viral persistence and disease progression. This study aims to find out relationship between levels of C4 in serum and its functional SNPs with response to treatment.

Methods: The study included 84 CHC patients who received treatment and 75 healthy controls. C4 expression, both at mRNA and protein level, was estimated by Real time and ELISA respectively. Its functional SNP’s genotyped by AS-PCR.

Results: The mean±S.D. baseline C4 levels between the disease and healthy cases was significantly different (1075.74±65.25 vs. 1593±24.55 ng/mL, p<0.001). The mean±S.D. baseline C4 levels of CC, GC and GG genotype of rs2857009 in the healthy group were 1540.97±7.87, 1599.53±11.75 and 1604.86±10.79 ng/mL respectively (p<0.001) whereas the levels in the CHC group were 1022.81±32.95, 1058.19±55.02 and 1150.26±14.64 ng/mL respectively (p<0.001). CC genotype resulted in decreased C4 mRNA levels compared to GG genotype in healthy group (3.81 fold) and CHC group (1.4 fold).

Conclusion: The CC genotype of rs2857009 is associated with reduced expression of C4, both at mRNA and protein level. The C4 serum level at baseline and total protein were found to be independent predictors for treatment response. New predictive score using the above factors, a value of ≥0.542 was found to predict positive response to treatment. Increased age, rs2857009 SNP and HCV genotype were associated with disease progression.

LVH-29

Long-term use of tenofovir and entecavir in hepatitis B virus related cirrhosis

Sundeep Kumar Goyal , Ashok Kumar Jain, Vinod Kumar Dixit, Suneet Kumar Shukla, Jayant Ghosh

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India

Background and Aims: Limited data is available from India on outcome and efficacy of tenofovir and entecavir in hepatitis B-related cirrhosis when used from prolonged time. We investigated the long-term efficacy and outcome of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis.

Methods: We retrospectively analyzed laboratory and clinical data of 400 HBV related cirrhotic patients without access to liver transplantation, which were treated with tenofovir/entecavir therapy at University Hospital’s Gastroenterology Services beginning in January 2007. Two hundred and ten (52.5 %) patients had at least one of the components of decompensation at baseline. Two hundred and twenty (55 %) and 180 (45 %) patients were initiated tenofovir and entecavir, respectively. Follow up period was 45 (12-68) months or tenofovir and 36 (11-60) months for entecavir.

Results: At end of 1-year levels of HBV DNA <20 IU/mL were achieved in 91.88 % and 88.88 % of patients and alanine amino-transferase normalized in 54.54 % and 55.55 % of patients who received tenofovir and entecavir, respectively. At last visit, Child–Turcotte–Pugh scores improved among 29.5 % of patients who received tenofovir, 25 % who received entecavir, and remains stable in 61.9 % and 65 % patients respectively in both groups. The 5-year cumulative rate of liver decompensation, hepatocellular carcinoma and cirrhosis related complications were 3.1 %, 1.9 % and 2.1 % with annual incidence of 0.88 %, 0.35 % and .55 % per person-year respectively.

Conclusion: Tenofovir and entecavir are effective and potent drugs for prolonged treatment of HBV cirrhosis patients and improve over all clinical course too.

LVH-30

Demographic profile and real life host, disease and viral predictive factors of response in patients with chronic hepatitis C virus infection at a tertiary care hospital in North India

Sreejith Vasudevan , Shalimar, Amit Kavimandan, Nancy Kalra, Baibaswata Nayak, Bhaskar Thakur, Prasenjit Das, Siddhartha Datta Gupta, Subrat Kumar Panda, Subrat Kumar Acharya

Department Gastroenterology, All India Institute of Medical Sciences, New Delhi 110 029, India

Objectives: Standard of care for chronic hepatitis C (CHC) in India is peginterferon and ribavirin (RBV). The real-life-picture of response to treatment is unclear. Primary objective was to study the demographic profile and assess-real-life-SVR rates in CHC patients. Secondary objective was to assess predictors of response.

Methods: Consecutive patients with CHC were included in this retrospective and prospective observational study. Detailed clinical history, risk factors, and predictive factors of response were noted. Patients were treated with peginterferon α2b (1.5 μg/kg/week) and RBV (12 mg/kg/day) for 6 to 18 months based on response.

Results: Two hundred and eleven patients were included, mean age 40.6±12.3 years, 144 (68 %) were males and 71 (34 %) had compensated cirrhosis. Commonest risk factor for acquiring CHC was previous transfusion and surgery (51 %). Genotype 3 (72 %) was most common followed by genotype 1 (23 %). Overall SVR rates were 64 % in intention to treat (ITT) group and 71 % in per-protocol (PP) group. In ITT, SVR was 66.5 % for genotype 3 and 61.2 % for genotype 1. In PP, SVR rates for genotypes 3 and 1 were 76.5 % and 62.5 % respectively. Noncirrhotics had better SVR rates compared to cirrhotics (76 % vs. 41 %, p2 were predictors of low SVR.

Conclusions: Genotype 3 was the commonest HCV genotype. The commonest source was previous transfusion and surgery. SVR rates for genotype 3 and non-genotype 3 were similar. Predictors of nonresponse were high BMI, insulin resistance, advanced fibrosis and inadequate compliance.

LVH-31

Cross sectional study of prevalence of hepatitis B and hepatitis C infection in a rural village of Maharashtra

Prasad Bhate , Naimish Saraf, Chetan Rathi, Meghraj Ingle, Aniruddha Phadke, Prabha Sawant

Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and Hospital, Sion, Mumbai 400 022, India, and Siddhakala Ayurved Mahavidyalay, Sangamner, India

Introduction: Hepatitis B virus (HBV) infection is leading health problem globally. There is limited data of epidemiology of hepatitis B in community more so in rural population. Hepatitis B and hepatitis C share a common risk factors and common mode of transmission, so it is rationale to study prevalence of these two together.

Material and Methods: This was a prospective community based cross sectional study. Written valid informed consent was taken from all the subjects. Study proforma was filled. Collected samples were subjected to card test for HBsAg and anti-HCV antibodies. All the positive card tests were confirmed by ELISA.

Observation and Results: Out of 2,400 subjects approached, 1,833 (47.41 % male) agreed to participate. Total 17 (8 male and 9 female) subjects were positive for HBsAg. None of the subjects was positive for anti-HCV antibody. Point prevalence for HBsAg positivity was 0.92 %. None of the subject’s age less than 10 year (number 287) and more than 51 year were positive for HBsAg. Being healthcare worker and having tattoo were significantly associated with HBsAg positive results. Nose and ear piersing was reported by almost everybody and was not significantly associated with HBsAg positivity. History of blood or blood product transfusion, I/V drug abuse, multiple sexual partners, unsafe Injections, hemodialysis and any h/o surgery was not associated with HBsAg positivity. History of male to male sex, acupuncture, organ transplant was not given by any of the participants.

 

Present in HBsAg positive

Present in HBsAg negative

p value

Healthcare workers

3

5

0.001

Tatto

3

73

0.03

Nose or ear piercing

16

1794

0.1150

Unsafe injections

5

512

1

Any h/o surgery

3

90

0.208

Blood or blood product transfusion

1

15

0.139

I/V drug use

0

4

1

Multiple sexual partners

0

10

1

Male to male sex:

0

0

1

Accupuncture

0

0

1

Hemodialysis

0

3

1

Organ transplant

0

0

1

Institutionalized persons

0

0

1

Conclusion: Seroprevalence of HBsAg in rural population of Maharashtra was 0.92 % and none of the 1,833 subjects was positive for anti-HCV antibody. Healthcare workers and having tatto was significantly associated with HBsAg positivity. This underscores the importance of universal precautions in healthcare workers.

LVH-32

Role of partial splenic artery embolization in a patient with hepatitis C cirrhosis of liver prior to antiviral therapy

Dhaval Gupta, Mallanagoud Patil , Chetan Rathi, Amol Khot, Aniruddha Phadke, Prabha Sawant

Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai 400 022, India,

Leukopenia and thrombocytopenia secondary to hypersplenism is a major limitation for standard dose of antiviral therapy in hepatitis C cirrhosis patient. We report a case of hepatitis C cirrhosis with severe leukopenia and thrombocytopenia who was treated with partial splenic artery embolization (PSAE). A 19-year-old female patient was admitted with hepatitis C cirrhosis. Lab tests showed severe leukopenia and thrombocytopenia. Due to high risk of splenectomy, hypersplenism was treated with PSAE. Peripheral blood counts increased significantly after partial splenic artery embolization. Post embolization patient developed abdominal pain, fever, ascites and pleural effusion. This was managed conservatively with antibiotic, IV fluids and analgesic. Post that patient was started on standard doses of PEG IFN and ribavarin. Patient completed 24 weeks of therapy with achievement of RVR and EVR. Peripheral blood counts were maintained throughout course of treatment.

Conclusion: PSAE can be successfully used to treat severe leukopenia and thrombocytopenia in patients with cirrhosis and hypersplenism. However patient selection has to be stringent and risk of complications explained to the patient.

LVH-33

Sequential therapy with pegylated interferon-alpha 2b and tenofovir versus tenofovir monotherapy in HBeAg positive chronic hepatitis B- A prospective pilot study

Ankur **dal , Manoj Kumar, Shiv Kumar Sarin

Department of Hepatology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Introduction: Current treatment strategies for HBeAg-positive patients with chronic hepatitis B (CHB) are largely ineffective in achieving sustained response in a majority of patients. Simultanoeus combination of interferon and nucleoside analogues has shown conflicting benefits. We have earlier shown that viral load reduction followed by immune modulation by interferon as a sequential therapy for 12 months helps improve the seroconversion. In the search for improved therapies, we evaluated the efficacy and safety of sequential therapy using tenofovir and pegylated interferon alfa 2b for the treatment of hepatitis B e antigen (HBeAg)-positive CHB.

Methods: We conducted a prospective randomized study in patients with previously untreated HBeAg (+) CHB with moderately elevated ALT (48-200 IU/mL). All patients received tenofovir (300 mg/day) for 12 weeks (lead-in-period). At 12 weeks, patients were randomly assigned to receive either tenofovir plus PEG-Interferon a2b 1.5 mcg/kg/weekly for 24 weeks (sequential therapy, ST) or tenofovir monotherapy (TM). Daily tenofovir was continued till primary end-point; i.e. HBsAg loss. Secondary end-points were rate of ALT normalization, HBeAg seroconversion and undetectable HBV DNA at 52 weeks. Sustained virological response (SVR) [defined as HBeAg (-) and undetectable HBV DNA 24 weeks post ST or TM] was also determined.

Results: Out of 114 HBeAg (+) CHB patients screened from January 2011 to April 2013, 60 eligible patients were randomized into two treatment groups (ST: TM=1:1). Their mean age (31.78±12.76 years vs. 37.65±12.54 years; p value-0.301), gender (M:F=25:5 in each group) and fibrosis stage (F >2, SM vs. TM=20 % vs. 40 %; p-0.141) were comparable. None had decompensated cirrhosis. There was no difference in ALT [67 vs. 77.5 IU/mL; p-0.595] and HBV DNA (6.93 log10 vs. 6.07 log10; p-0.07] at baseline and at week 12. After 52 weeks of therapy, 60 % patients in ST group had normal ALT as compared to 30 % in TM group [p value- 0.02]. Those receiving ST also had significantly higher HBV DNA loss (80 % vs. 53.3 %; p-0.028) with a mean HBV DNA reduction of 6.70+1.64 log10 vs. 4.43+2.44 log10; p< 0.001 respectively. Although, 6 patients (0 in MT group) in the ST group had HBeAg seroreversion, patients on ST had higher HBeAg seroconversion (53.3 % vs. 23.3 %; p-0.017) at 52 weeks. Overall, 43.3 % patients achieved SVR in the ST group. Three patients (10 %) on ST achieved HBsAg loss compared with MT (1 patient, 3.3 %) by 52 weeks. Factors associated with HBsAg loss included higher ALT at baseline (OR:11.5; p-0.05) and female sex (OR:16; p-0.04). No patient had treatment related major adverse effect requiring discontinuation of therapy.

Conclusion: Sequential therapy with tenofovir and PEG-IFN a2b may provide rapid biochemical and virological response in selected HBeAg(+) chronic hepatitis B patients, although long-term follow up trials are needed to assess for sustained durable response.

LVH-34

A comparative study of the antiviral efficacy and safety of entecavir versus placebo in HBeAg-positive pediatric subjects with chronic hepatitis B

Rahul Bargaje , D Kelly 1 , M M Jonas 2 , K Schwarz 3 , M H Chang 4 , D Oraseanu 5 , E Sokal 6 , N Assy 7 , L Reynolds 8 , A Thiry 8 , P Ackerman 8

1Birmingham Children’s Hospital, Birmingham, UK, 2Boston Children’s Hospital, Boston, MA, USA, 3Johns Hopkins Children’s Center, Baltimore, MD, USA, 4National Taiwan University Hospital, Taipei, Taiwan, 5Grigore Alexandrescu Hospital for Children, Bucharest, Romania, 6Cliniques Universitaires Saint-Luc, Bruxelles, Belgium, 7Ziv Medical Center, Safed, Israel, 8Bristol-Myers Squibb, Wallingford, CT, USA

Aim: To assess the safety and efficacy of entecavir (ETV) in children and adolescents with CHB at week 48.

Method: A comparative, randomized, double blind, placebo-controlled, multicenter study, nucleos(t)ide-na±ve children and adolescents with CHB were randomized 2:1 to receive ETV or placebo for 96 weeks. The primary end-point was the proportion of subjects in the primary cohort with combined HBV DNA <50 IU/mL and HBeAg seroconversion at week 48 (non-completer=failure). Secondary end-points included the proportion of subjects with HBV DNA <LOQ, and HBeAg seroconversion at week 48.

Results: One hundred and eighty subjects were randomized and treated with ETV (n=120) or placebo (n=60). A significantly higher proportion of ETV-treated subjects achieved the primary end-point of combined HBV DNA <50 IU/mL and HBeAg seroconversion compared with those receiving placebo. The proportions of subjects who achieved key secondary end-points of HBV DNA <50 IU/mL, ALT normalization, and HBV DNA<LOQ were also significantly higher in the ETV group. A higher proportion in the ETV group experienced HBeAg seroconversion, although this was not statistically significant. Few subjects in either group achieved HBsAg loss (2 % in each), and one ETV-treated subject achieved HBsAg seroconversion at week 48. Among all treated subjects, SAEs occurred in 11 subjects (ETV, n=4; placebo, n=7); none were considered related to study drug.

Conclusions: ETV demonstrated superior antiviral efficacy to placebo in pediatric subjects with CHB, with a safety and tolerability profile that was comparable to adult subjects. These results support the use of ETV as a therapeutic option in children and adolescents with CHB.

LVH-35

WITHDRAWN

LVH-36

Identification of Indian sub-continent as hotspot for HCV genotype 3a origin by Bayesian evolutionary reconstruction

Manish Chandra Choudhary 1,2 , Vidhya Natarajan 1 , Priyanka Pandey 3 , Ekta Gupta 3 , Shvetank Sharma 1 , Rachana Tripathi 4 , M Shesheer Kumar 4 , Syed N Kazim 2 , Shiv K Sarin 1

1Department of Research, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, and 2Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia UniversityIslamia, New Delhi 110 025, India 3Department of Virology, Institu

Background: Recent emphasis in hepatitis C virus (HCV) evolutionary biology has focused on analysis using core, E1/E2 and/or NS5b regions, with limited appreciation of full length genome. While HCV genotypes have been described as endemic in the Indian subcontinent, there has been no confirmation at the molecular evolutionary level of these genotypes. We have attempted here to determine the status of Indian HCV genotype 3a sequences in relation to similar genotypes from other parts of the world.

Methods: Cloning, sequencing and molecular characterization was performed on 9 Indian sequences and comparative analyses were performed with 46 sequences from other countries. Evolutionary-rate and molecular-clock hypothesis testing was addressed by Bayesian MCMC.

Results: Genetic analysis of full length genome revealed two hypervariable regions (HVR) in E2 region - HVR496 and HVR576, with a variable 5-8 amino-acid insertion sequence and a putative N-glycosylation site. Phylogenetic analysis revealed a divergence resulting in 2 distinct clades: clade-1 represented by HCV 3a subtype and clade-2 represented by other 3 subtype genomes. Clade-2 shows earlier divergence than clade-1. Analysis revealed that genotype 3a genomes from India roots out first (~99 years ago) in clade1. Bayesian skyline plot analysis revealed an increase in effective number of infections from 1940s to 1990s, followed by a gradual decrease after 2000.

Conclusions: Genotype 3a sequences appear to have originated in India and later dispersed to United Kingdom around mid 1940s, most likely around the time of Indian independence and World War II.

LVH-37

Assessment of knowledge, attitude and practice towards hepatitis B among nursing staff of Narayana Medical College, Nellore

Harsha , Harish Kumar, Vamsidhar Reddy, Rahul, M G Srinivas, K R Thankappan

Narayana Medical College, Chinthareddypalem, Nellore 524 003, India

Aim: To assess knowledge, attitude and practice among nurses in tertiary care hospital, Nellore towards their awareness of hepatitis B infection, it's prevention and control.

Methods: A cross sectional study was conducted on 250 staff nurses working in Narayana General Hospital by means of a questionnaire for assessment of their knowledge and practices on hepatitis B.

Results: Among 250 staff nurses, 219 (87.6 %) answered the questionnaire. The mean of correct answers to the knowledge questions in 72.14 %, to the attitude questions is 68.88 % and to practice questions is 71.6 %. In our study group 19.17 % know that infection is not transmitted by food prepared by person infected with hepatitis B. Only 54.34 % were willing to provide services to hepatitis B infected patients and 76.17 % of them have attended health education programmes on hepatitis B earlier.

Conclusion: The overall scoring of KAP study among our study group is around 70 % which means they require further educational programmes mainly regarding modes of transmission, vaccination, it's protective effect and availability of post exposure prophylaxis so as to lower the discriminative attitude towards people infected with hepatitis B.

LVH-38

WITHDRAWN

LVH-39

Prediction model for mortality in hepatitis E virus related acute liver failure during pregnancy

Sheetal Sharma , Ashok Kumar, Sudha Prasad, Sarita Agarwal, Shashi Sharma

Departments of Obstetrics and Gynecology, and Biochemistry, Maulana Azad Medical College and associated Lok Nayak Hospital New Delhi 110 002, India and Institute of Cytology a

Aim: To establish a prognostic model based on pregnant patients to predict mortality in HEV-related acute liver failure (ALF) based on biochemical and hemotogical parameters.

Method: A total of 73 pregnant patients with hepatitis E virus (HEV) related ALF based on standard clinical and biochemical criteria from antenatal wards and medicine wards of Lok Nayak Hospital during the period 2008-2013 were recruited. The ALF disease group was further divided on the basis of the outcome of the disease into nonsurvival group (ALF-NS) and survival group (ALF-S).

Results: The mortality rate in HEV-related ALF pregnant patients was 63.01 % (46/73). Univariate analysis showed that alkaline phoshpatase, INR, serum albumin and viral load were significantly different among survival group and nonsurvival group. Multivariate analysis revealed that serum alkaline phosphatase and INR were independent predictors of mortality. Incorporating these significant variables, a new score predicting mortality risk during pregnancy was derived. A receiver operating characteristic curve analysis for new score revealed an area under curve (AUC) of 85 % with 76.09 % sensitivity and 88.89 % specificity. The new score was significantly different between survival group and nonsurvival group (p<0.001).

Conclusion: ALP and INR are the prognostic factors for mortality and can be used for risk stratification. The established prognostic model for HEV-related ALF during pregnancy had superior specificity and AUC compared to MELD.

Liver – Others

LO-01

Intensive care unit admissions in cirrhotics

Mayank Jain, Sandeep Ware, Amit Bundiwal, Shohini Sircar, Ajay K Jain

Choithram Hospital and Research Centre, Manik Bagh Road, Indore 452 014, India

Aim: 1. To study the common reasons for admission in ICU among cirrhotics. 2. To study the requirement of mechanical ventilation, hemodialysis and their impact on outcome in these patients.

Methods: Records of all cirrhotic patients who were admitted in ICU of our hospital from March 2013 to March 2014 were obtained. Patients admitted in other units and those who left against medical advice were excluded. The data was analyzed for age, sex, MELD score for severity of liver disease, requirement of hemodialysis and mechanical ventilation, duration of stay and outcome.

Results: A total of 57 patients were admitted to ICU during the study period. The mean age was 34.9 years (22-70 years) and male:female ratio was 16:3. The etiological factors for cirrhosis were-alcohol (33), hepatitis C (9), hepatitis B (06), autoimmune hepatitis (2), cryptogenic cirrhosis (4) and Wilson’s disease (3). Forty-two patients improved and 15 patients died during the same admission. The main reasons for ICU admissions were GI bleed (30), hepatic encephalopathy (30), infection (24), renal dysfunction (21), multiorgan failure (3), severe alcoholic hepatitis (5), hepatocellular carcinoma (3), hepatic hydrothorax (2), cellulitis (4) and diabetic ketoacidosis (1). The mean MELD score was 26.9 (13-39). Forty-five patients were admitted directly to ICU and twelve were shifted from wards. Twelve patients required mechanical ventilation and six required hemodialysis. The average duration of stay was 2.64 days. Patients who expired during the stay had a higher MELD score (29.8 vs. 24), had renal dysfunction (80 %) and required mechanical ventilation (80 %). All patients with hepatocellular carcinoma and MODS died during the same admission. All patients who required mechanical ventilation also expired.

LO-02

A study of metabolic parameters in non-diabetic patients of fatty liver who do not consume alcohol

T Agarwala , G Ray

B R Singh Hospital, Sealdah, Kolkata 700 014, India

Background: Fatty liver is common in patients with diabetes mellitus or ethanol consumers. Though its causative metabolic factors in such patients are well delineated, risk factors in nondiabetic teetotaller persons who constitute a small but definite percentage of fatty liver patients in India are not defined.

Methods: In this case control study, the metabolic parameters of 50 non-diabetic teetotaller patients (Gr 1) were compared with those of 50 patients of IGT (impaired glucose tolerance) (Gr 2) and 50 overt diabetics (Gr 3). Fatty liver was diagnosed on USG/CT scan abdomen and NAFLD fibrosis score was calculated to assess severity. The studied parameters were age, sex, BMI, FBS, fasting plasma insulin, complete lipid profile, HOMA-IR, HBA1c whose correlation with NAFLD fibrosis score was assessed by univariate and multivariate analysis with significance set at p<0.05. By the latter, factors affecting development of IGT and diabetes in comparison to the cases were also studied.

Results: Total cholesterol (R2 0.7, p 0.01) and triglyceride (R2 0.75, p 0.01) were the only significant contributors of fatty liver in Gr 1. When Gr 1 and 2 were analyzed together with IGT as outcome variable, high HBA1c (OR 6.88 CI 1.56–30.3) and triglyceride (OR 1.08 CI 1.02–1.15) was associated with development of IGT. When Gr1+2 was compared with Gr3 with diabetes mellitus as outcome variable, high HBA1c (OR 4.05 CI 1.82–9.02) and HOMA-IR (OR 1.21 CI 1.07–1.36) was associated with development of diabetes mellitus.

Conclusion: Dyslipidemia is associated with fatty liver in nondiabetic teetotallers. p<0.05. By the latter, factors affecting development of IGT and diabetes in comparison to the cases were also studied.

LO-03

Risk factors for in-hospital mortality in cirrrhotic patients admitted with sepsis

G Paul Cheruvathur , P V Mashhood, George Peter, N Premalatha, K R V Kumar

Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram 695 011, India

Background: Bacterial infections are much more common in patients with cirrhosis than in the general population. Infection is more frequent in patients with decompensated cirrhosis than in those with compensated cirrhosis. Patients with cirrhosis have increased risk to develop sepsis, sepsis-induced organ failure, and sepsis-related death.

Aim: The aim of the study was to determine factors associated with increased in-hospital mortality in cirrhotic patients admitted with sepsis.

Materials and Methods: All consecutive patients with a confirmed diagnosis of cirrhosis with sepsis admitted from November 2012 to April 2014 were included in this study. The diagnosis of liver cirrhosis was based on medical history, physical examination, biochemical parameters, ultrasound findings and/or liver biopsy. Sepsis was defined as systemic inflammatory response syndrome (SIRS) in response to suspected or documented infection.

Results: There were a total of 76 cases. Males constituted 55 (72.4 %) of study population. The mean age of the study population was 52.29±12.18 years. The most common etiology of cirrhosis was alcohol 38 (50 %). The mean Child’s score was 9.64± 2.20 and MELD score was 16.30±4.97. The most common infection identified was SBP 35 (46.1 %). More than one site of infection was identified in 26 (34.1 %). The in hospital mortality rate was 28/76 (36.8 %). Factors found to be significantly associated with in-hospital mortality on multivariate analysis were CHILD-C status, MELD score ≥17, more than one site of infection and culture positivity. In predicting in-hospital death, Child-Pugh score has an area under the ROC curve of 0.797 with the optimum cut-off at 10 points and above with sensitivity 95.7 % and specificity 64.2 %, and for MELD score was 0.876, with the optimum cut-off at 17 points and above with sensitivity 82.6 % and specificity 79.2 %.

Conclusions: Cirrhotic patients with sepsis have a high risk for mortality. Child’s C cirrhosis, more than one site of infection, culture positivity and high MELD (>17) score were associated with worse outcome. These patients should be identified early and treated aggressively from the outset.

LO-04

Profibrogenic transforming growth factor-beta1 (TGF-β1) polymorphism in alcoholic liver disease

K Pratibha 1 , Sri Manjari 2 , O Vandana 1 , A Venkateshwari 2 , A Jyothy 2 , Pratibha Nallari 4 , M Uma Devi 1 , M Ramanna 1 , I Bharani 1 , P Shravan Kumar 1

1Department of Gastroenterology, Gandhi Hospital, Secunderabad 500 025, India, 2Institute of Genetics and Hospital for Genetic Diseases, and 3Department of Genetics, Osmania University, Hyderabad 500 00, India

Background: Alcohol induced liver disease or alcoholic liver disease (ALD), a complex trait, encompasses a gamut of pathophysiological alterations in the liver due to continuous exposure to a toxic amount of alcohol (more than 80 g per day). Of all chronic heavy drinkers, only 15 % to 20 % develops hepatitis or cirrhosis concomitantly or in succession. Several studies revealed that inter-individual as well as inter-ethnic genetic variation is one of the major factors that predispose to ALD.

Introduction: Ethanol exerts its detrimental effects by various means: Directly via toxic metabolites, and indirectly by affecting the gut barrier leading to elevated levels of endotoxins in the blood challenging the liver. These factors, together with the resulting inflammatory and profibrogenic cytokine production, drive the organ's response, characterized by activation of hepatic stellate cells. Recent evidence argues for other cell types besides hepatic stellate cells, including hepatocytes, as additional sources of fibroblasts producing extracellular matrix and to be responsible for scar formation. Besides mediating hepatocyte apoptosis, TGF-β additionally induces fibroblastoid transdifferentiation. This process is accompanied with loss of epithelial marker proteins and upregulation of fibrosis related proteins. These findings challenge the current view of the role of TGF-β in liver fibrosis.

Transforming growth factor- β1 (TGF-β1) is one of the key cytokines in extracellular matrix production and acts at different levels to increase collagen deposition. Single nucleotide polymorphisms (SNP) in the promoter of TGF-β1 cytokine gene are known to alter the production of this important cytokine.

Objective: We investigated the functional significance of TGF-β1 (C-509T) promoter SNP in alcoholic liver disease.

Material and Methods: The study group was composed of 30 patients with ALD and 30 normal controls referred to the Gastroenterology Unit of Gandhi Hospital. Information regarding the epidemiological factors such as age, sex, disease duration and severity, addictions such as smoking and alcohol has been collected from patients and control subjects. The polymorphism for TGF-β1 (C-509T) allele was genotyped using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) method, followed by agarose gel electrophoresis.

Results: The frequencies of genotypes in promoter of TGF-β1 were CC 48 %, CT 32 % and TT 20 % in ALD patients and CC 52 %, CT 42 % and TT 6 % in control subjects. There is an increase in the frequency of TT genotype frequency in the disease group compared to control subjects [1.592 (0.68-3.72), p=0.327].

Conclusion: The T homozygote and T allele, which are associated with higher production of TGF-β1, are thus associated with higher risk of alcoholic liver disease. Hence the TGF-β1 (C-509T) promoter polymorphism is associated with the prognosis of the disease. However large number of samples has to be analyzed to confirm the results.

LO-05

Cytopathological changes associated with hepatocyte senescence during evolution of cirrhosis and monitoring senescence in cell culture system (Huh7 cells)

Bijoya Sen 1 , Chhagan Bihari 2 , Archana Rastogi 2 , Nirupama Trehanpati 1 , Shvetank Sharma 1 , Shiv K Sarin 3 , Gayatri Ramakrishna 1

1Departments of Research, 2 Pathology, and 3Hepatology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Purpose: Cellular senescence is a permanent growth arrest condition involved in process of ageing and tumor suppression. Identification of senescent cells is challenging particularly in primary tissues. Purpose of this study was to evaluate cytopathological features associated with senescence in conditions of cirrhosis and following doxorubicin treatment in hepatocellular carcinoma cell line (Huh7).

Methods: Huh7 cells were treated with low dose of doxorubicin (2uM, 2 hr) to induce premature senescence, which was evaluated by morphology (bright field microscopy and electron microscopy), SA-β-galactosidase staining and p21 expression. Liver sections from precirrhotic (Metavir stage 3) and cirrhotic conditions (Metavir stage 4) were evaluated for presence of senescent like cells by combination of p21 expression together with cytomorphological feature of nuclear enlargement and vacuolation.

Results: Doxorubicin treated Huh7 cells showed enlarged cytomorphology, multinucleation, and positivity for SA-β-galactosidase activity coupled with G2/M phase cell cycle arrest indicative of premature senescence. Huh7 senescent cells showed accumulation of autophagic vacuoles, prominent lysosomes and mitochondrial-endoplasmic reticulum coupling. Compared to precirrhotic condition, the hepatocytes in cirrhotic liver showed higher percentage of p21 nuclear immunoreactivity with prominent nuclear vacuolation (precirrhotic 2.74+0.33, cirrhotic 7.35+1.6; p<0.006) and increased nuclear volume (precirrhotic 147.46+9.28, cirrhotic 202.32+10.2, p<0.0005). In cirrhosis p21 expression was more around periseptal region whereas in precirrhosis, it appeared uniform throughout the lobule.

Conclusions: Premature senescence in both in vitro and in vivo conditions showed cytomorphological changes indicative of adaptive response of senescent cells. Additionally increased p21 expression coupled to nuclear vacuolation appears as a good marker to identify a senescent cell.

LO-06

Essential role of tumor necrosis factor alpha (TNF-α) polymorphism in alcoholic liver disease

I Bharani 1 , K Sri Manjari 2 , O Vandana 1 , A Venkateshwari 2 , A Jyothy 2 , Pratibha Nallari 4 , M Uma Devi 1 , M Ramanna 1 , Pratibha 1 , P Shravan Kumar 1

1Department of Gastroenterology, Gandhi Hospital, Secunderabad 500 025, 2Institute of Genetics and Hospital for Genetic Diseases, and 3Department of Genetics, Osmania University, Hyderabad 500 016,  India

Aim: We investigated the functional significance of TNF-α promoter SNP in alcoholic liver disease.

Materials and Methods: The study group was composed of 30 patients with ALD and 30 normal controls referred to the Gastroenterology Unit of Gandhi Hospital. Information regarding the epidemiological factors such as age, sex, disease duration and severity, addictions such as smoking and alcohol has been collected from patients and control subjects. Genoty** was carried out by tetra-primer ARMS PCR followed by agarose gel electrophoresis.

Results: The genotype distribution of TNF-α (-308 G/A) promoter region were 35 % (G/G), 33 % (A/G) and 32 % (A/A) in ALD compared to 50 % (G/G), 36 % (A/G), and 14 % (A/A) in control subjects. A variation [1.88 (0.84-4.28), p=0.134] was observed with respect to the genotypic and allelic distribution in the disease group when compared to control subjects.

Conclusion: The present study revealed a significant association of the TNF-α gene promoter polymorphism with alcoholic liver disease. Thus, TNF-α genotype may be postulated to play a role in many of the metabolic complications and the liver injury of alcoholic liver disease.

LO-07

Amebic liver abscess: Experience from central India

Mohd Talha Noor, Satyarth Chaudhary , Neeraj Jain, Bhagwan Singh Thakur

Department of Gastroenterology, Sri Aurobindo Institute of Medical Sciences, Indore 543 111, India

Introduction: Amebic liver abscess (ALA) is a common space inflammatory lesion of the liver in develo** countries. It is associated with high mortality and morbidity. ALA is common in India but limited data is available from central India.

Material and Methods: Medical records of 60 inpatients of diagnosed ALA from January 2013 to July 2014 were retrospectively reviewed. Diagnosis of ALA was based on ultrasonography, positive serum IgG antibodies to Entameba histolytica using ELISA technique and or anchovy sauce appearance of abscess fluid. Indication for aspiration are abscess of >6 cm or volume >300 mL, thin (<1 cm) rim or no discernible hepatic parenchyma around any part of circumference of the abscess, left sided abscess, lack of response to medical therapy. All patients were given intravenous ceftiaxone 1 gram twice daily and intravenous metronidazole (40 mg/kg/day) for 14 days.

Results: Mean age was 40.15±13.67 years, male to female ratio was 7.5:1. Majority of patients presented with fever (91.66 %), abdominal pain (93.33 %) and hepatomegaly (95 %), 41 patients (68.33 %) were alcoholic. Leukocytosis, hypoalbuminemia, hyponatremia and hypoglycemia were present in 73.33 %, 83.33 %, 53.33 %, 30 % patients respectively. Abscesses were predominantly in right lobe (78.33 %), solitary (65 %). Twenty-six patients (43.33 %) could be managed medically while 14 patients (23.33 %) required percutaneous needle aspiration. Twenty patients (33.33 %) were taken up for percutaneous pigtail catheter drainage. Six patients (10 %) had ALA rupture, 3 patients (5 %) required laparoscopic surgical drainage. Mean duration of hospital stay was 11.08±4.91 days. Mortality was 3.33 %.

Conclusion: ALA should be suspected in patients presenting with right upper abdominal pain and fever. Early diagnosis and treatment leads to clinical improvement and prevents complications.

LO-08

Risk of intravenous contrast nephropathy in cirrhosis liver patients: A prospective observational study

Mashhood Padincharepurathu Villyoth , George Peter, Paul Cheruvathoor, Tony Joseph, Suthanu Bahuleyan, Prasanth K Sobhan, Premalatha Narayanan, Kattoor Ramakrishnan Vinayakumar

Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram 695 011, India

Background: Cirrhotic patients are prone to worsening of kidney function following intravenous contrast administration, due to reduction in effective circulating volume. However, whether liver cirrhosis is an added risk factor has not been well studied. This study aims to evaluate the risk of acute kidney injury (AKI) in cirrhotic patients receiving radiocontrast agents.

Methods: We performed a prospective observational study with a parallel control group. Thirty cirrhosis liver patients who underwent intravenous contrast CT imaging abdomen in Department of Medial Gastroenterology during the period January 2013 to April 2014 were selected. Age, sex, CTP, SBP, diuretic and alcoholic hepatitis matched control group of cirrhosis liver patient not received radiocontrast were taken from same patient population. AKI is defined as more than 50 % increase in serum creatinine from baseline after 48 hours.

Results: Total of 30 cases and controls were selected out of which 24 patients were male and 6 patients were females. Median age of cases was 48.5 years. Median CTP score was 10. Ninety-three percent of cases and control had ascites. Seventy-two percent of patients were taking diuretics. Twenty percent of our patients who received contrast developed AKI where as twenty three percent of control group who did not receive contrast developed AKI (p 0.754).

Conclusion: Our results suggest that in cirrhosis liver patients, administration of radiocontrast agents per se do not associated with worsening of renal function.

LO-09

Study the expression of microRNAs in hepatitis B virus related hepatocellular cacrinoma

Dipu Bharali , Premashis Kar

Department of Medicine, Maulana Azad Medical College, Bahadur Shah Zafar Marg, Delhi Gate, Delhi 110 002, India

Background and Aims: MicroRNAs are small, noncoding RNAs about 22 nt long that negatively regulate gene expression at the post-transcriptional level. microRNA deregulation and apolipoprotein plays a vital role in human hepatocellular cacrinoma (HCC). This study is designed to find out differential expression of cancer related miR-21 and miR-122 and in HBV associated HCC.

Methods: Total RNA was extracted from blood of 25 patients of chronic hep B without liver cirrhosis and HCC, 25 patients of liver cirrhosis of CHB without HCC, and 45 with CHB HCC and 10 healthy control subjects using miRNEasy Qaigen kit. Expression changes of miRNAs were examined by c-DNA amplification using RT-stem loop primer followed by real-time RT-qPCR using ABI Taqmaan chemistry.

Results: The results have been obtained as fold changes (Ct value) relative to control conditions after normalizing against RnbU6 reference gene. Micro RNA miR-21 is upregulated in HBV HCC compared with healthy control subjects (p<0.05) and miR-122 have been found to be shown downregulation in relation to internal control RNU6B in HCC in comparison to background healthy control (p<0.05).

Conclusion: microRNA miR-122 and miR-21 was expressed differentially in HBV HCC in comparison to healthy control subjects. The expression differences in the regulation of miRNAs in carcinogenesis may be worthy of further study.

LO-10

Clinical profile and factors associated with liver enzyme abnormalities among HIV-infected persons

Ashok Mohite , Pravir Gambhir , Dharmesh Shah, Sunil Pawar, Quais Contractor, Pravin Rathi

Department of Gastroenterology, Topiwala National Medical College and B Y L Nair Hospital, Mumbai Central, Mumbai 400 008, India

Background: HIV infected patients are experiencing longer life expectancies, liver diseases has been recognized a major issue, data about etiology of deranged liver function is limited and is mostly from western countries.

Aims and Objectives: To study the clinical spectrum, potential cause(s) and predictors of mortality among HIV-infected patients with deranged liver function.

Materials and Methods: Ninety-eight HIV infected patients with deranged liver enzymes were prospectively evaluated for possible cause of liver disease. Equal number of HIV positive with normal LFT and HIV negative with normal LFT are evaluated.

Results: Out of 98 HIV patients with deranged LFT cause of liver dysfunction was found in 90 patients (90 %), 8 (10 %) patient remains undiagnosed. Most common diagnosis was drug induced (26 %) hepatitis B (20 %) and alcoholic liver disease 9 (18 %). Eight patents died during 1 month follow up. Most common causes of death were alcohol and HBV related liver disease. On univariate analysis predictors of mortality was raised WBC count, low CD4 count and high AST platelet ratio index (APRI). Raised serum triglyceride, low CD4 count, long duration of HIV and duration of ART was statistically significant in deranged LFT group compaired to control (p<.05).

Conclusions: Our study revealed that in HIV infected patient liver dysfunction is more common in patient with low CD4 count, long duration of HIV and ART treatment and mortality is increased in patient with high AST platelet ratio index (APRI) and raised WBC count.

LO-11

Acute liver failure due to organophosphorus poision

Sushant Sethi , Rasmirekha Behera.

Apollo Hospital, Bhubaneshwar 750 015, and Pharmacology, Institute of Medical Sciences and Sum Hospital, K-8, Kalinga Nagar, Bhubaneshwar 751 003, India

Background: Acute liver failure is the most dreaded complication of acute viral hepatitis, drugs, toxin and many other diseases affecting liver. While acetaminophen is the most commonly implicated drug in western world very few toxins were found to cause ALF in India. Organophosphorus poisioning frequently found in India causing CNS, cardiac and respiratory involvement. Isolated acute liver failure due to organophosphorus is rare. This case of acute liver failure who lost five of his family members due to consumption of food stuff in whom autopsy of viscera revealed organophosphorus is the lone member who survived. Case-33-year-old male presented with reeling of head and vomiting after consuming some home made food. On examination he was conscious, oriented and icteric, hemodynamics and urine output was normal, investigatins revealed serum bil-6.3/2.4 dmg, ALT-10, 225U/L, ast-12, 865u/l, PT-13.1/66.1, Sec (INR-8.89), tlc-5,000/cmm, creat-1.1 mg, serum ammonia-138m mol/L. Other infective markers for viral hepatitis, dengue, malaria and leptospira were negative. Within hour patient went into encephalopathy. Management-HE was managed in line of acute liver failure including ICU care, head elevation, mannitol, N-acetyl cystine, vitamin K, IV fluids, IV antibiotics and supportive treatment. Possibility of need of liver transplantation was discussed but family expressed inability to afford. He was not bleeding hence FFP not given. He started improving after 72 hrs and fully recovered within 10 days.

Conclusion: Organophosphorus can cause acute liver failure in isolation and patient of acute liver failure may survive without liver transplantation.

LO-12

Dynamic contrast enhanced MRI: Role in characterization of focal liver lesions

Sunil Pawar , , Abhinav  Ranwaka, Vinay Zanwar, Pravir Gambhire, Shenaz Saifi , Pravin Rathi

Departments of Gastroenterology and Radiology, Topiwala National Medical College and B Y L Nair Hospital, Mumbai Central, Mumbai 400 008, India

Background: Liver is principal site for primary malignancies and a major target for metastatic disease. The incidence of benign hepatic lesions is also comparatively high.

Aims and Objective: Study role of dynamic contrast enhanced MRI in characterization of focal liver lesions and correlate with histopathological findings.

Materials and Methods: MRI imaging of patients was performed on a Philips 1.5 Tesla MRI. Attempt was made first to decide whether a lesion was benign or malignant and then to choose one diagnosis from a list of possible differential diagnoses, gold standard being histopathological diagnosis.

Results: Thirty-one consecutive MRI images were analyzed. Histopathologically benign lesions were found in 45.16 % (14), malignant in 54.83 % (17). Sensitivity of MRI without dynamic images were 64.7 %, with dynamic images was 94.1 %. Specificity of both was 100 %. Inspite of the observed increase in accuracy, the results were statistically not significant, attributable to a small sample size. Distribution of benign lesions was simple cyst in 14.28 % (2), hydatid cyst 14.28 % (2), granulomatous lesion 7.14 % (1), hemangioma1 4.28 % (2), pseudolesion 21.42 % (3), abscess 14.28 % (2), FNH 7.14 % (1). Malignant lesions were HCC in 41.17 % (7), metastasis 35.29 % (6), cholangiocarcinoma 17.64 % (3). Size cannot distinguish between benign and malignant lesions. Younger the age benign causes were more frequent. Cystic lesions were all benign and solid lesions were predominantly malignant. All HCC showed either homogenous hyperintensity with rapid washout or diffuse heterogenous hyperintensity with rapid washout.

Conclusions: Use of dynamic post contrast MRI definitely improves the characterization of liver lesions in terms of specific diagnosis.

LO-13

Predictors of response and outcome to terlipressin in patients with hepatorenal syndrome

Vinit Sanjay Shah , Ashish Kumar, Praveen Sharma, Rinkesh K Bansal, Pankaj Tyagi, Naresh Bansal, Vikas Singla, Anil Arora

Departments of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, Old Rajender Nagar, Delhi 110 060, India

Background: Hepatorenal syndrome (HRS) has prodigious mortality and extremely poor prognosis. We conducted this prospective, observational, cohort study to determine the factors influencing HRS development and survival and predictors of response to terlipressin with outcome in terlipressin responders.

Methods: Cirrhotic patients were diagnosed with acute kidney injury (AKI) were enrolled. as per (IAC/ADQI) definition and evaluated as per the study protocol and patients receiving terlipressin were analyzed for terlipressin response perdictors.

Results: Three hundred and ninety-five consecutive cirrhotic patients with renal impairment enrolled. Out of these AKI patients HRS was seen in 85 patients (21.5 %). Terlipressin was given to 162 patients, 72 (44 %) patients responded to terlipressin as per the study definition. Ninety (56 %) patients were terlipressin nonresponders. HRS had the worst survival outcome. Significantly worst survival was seen in terlipressin nonresponders. Higher MELD score, low serum albumin, presence of SBP and presence of hypotension with inotrope requirement were more significantly associated with HRS/ATN development whereas HRS mortality did not get affected with infection related parameters. Presence of hypotension requiring inotropic support was the only factor on multivariate analysis to correlate with terlipressin nonresponse.

Conclusions: Development of HRS is associated with significantly reduced survival than other types of AKI in cirrhotics with especially dismal survival in terlipressin nonresponders. The terlipressin response rate in our cohort was 44 %. Development of hypotension with inotropic requirement was the single most important predictor of terlipressin nonresponse.

LO-14

Spectrum and short-term outcome of renal impairment in cirrhosis

Vinit Sanjay  Shah , Ashish Kumar, Praveen Sharma, Rinkesh K Bansal, Pankaj Tyagi, Naresh Bansal, Vikas Singla, Anil Arora

Departments of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, Old Rajender Nagar, Delhi 110 060, India

Background: Study attempted to classify acute kidney injury (AKI) and its outcome at 1 month and 3 months.

Methods: Cirrhotic patients with AKI enrolled. Cause, type of AKI and 1 and 3 months outcome studied.

Results: Three hundred and ninety-five patients included. In hospital mortality 154 (39 %), 226 (57.2 %) survived at 1 month, 173 (43.8 %) at 3 months. Infective focus in 190 (48.1 %) with SBP 84 (21.3 %) patients commonest. Ongoing diuretic use 150 (38 %) commonest noninfective precipitant. Three hundred and thirty patients (83.5 %) had at admission AKI and 89 (22.5 %) had in hospital AKI. RRT requirement in 120 (30.4 %). Volume responsive AKI (VRAKI) commonest 198 (50.1 %). Volume nonresponsive AKI (VNRAKI); hepatorenal syndrome HRS in 85 (21.5 %), acute tubular necrosis (ATN) 55 (13.9 %), 9 (2.3 %) acute glomerulonephritis (AGN), associated CKD 48 (12.2 %). Recurrent AKI 45 (11.3 %) with VNRAKI commonest 24 (53.3 %). VRAKI had best survival and ATN/HRS poorest. Survival significantly poor with ACLF, terlipressin nonresponse and recurrent AKI. Type of AKI related to MELD score, serum albumin, presence of SBP and hypotension with inotrope requirement. Presence of HE, low albumin and ATN/HRS significantly associated with death. Survival influenced by infection related parameters in VRAKI and not in ATN and HRS. The need for RRT requirement across all AKI groups was significantly influenced by the isolation of gram negative organisms.

Conclusions: AKI in cirrhosis associated with significantly high in hospital mortality, higher need for renal replacement therapy, progressively reduced 1 month and 3 month survival. VRAKI commonest with best survival but HRS/ATN have worst survival.

LO-15

Response guided ascitic tap in spontaneous bacterial peritonitis predicts outcome

Ashok Kumar Choudhury , Madhumita Prem Kumar, Devraj Gowda, Ankur **dal, Rakhi Maiwal, Chiranshu Vashistha, Shiv Kumar Sarin

Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: Spontaneous bacterial peritonitis (SBP) is the major and life-threatening infection in cirrhosis. Identification of risk factors, timing of antibiotic in relation to response are key to success without major development of resistant infection. Here we focused on serial ascitic tap for antibiotic response to predict the outcome of SBP.

Methods: All consecutive patients of decompensated cirrhosis diagnosed with spontaneous bacterial peritonitis admitted to hospital were analyzed retrospectively. The patient undergone ascitic tap after 48 hr in majority cases and on 5 th and 7 th day depending upon the clinical parameters.

Results: Total 161 patient of decompensated cirrhosis 141 (88 %), 12 % acute-on-chronic liver failure with mean age 50. Eight yrs (±11.8SD) and 82 % male. Ethanol was the most common etiology (n=64, 40 %), followed by cryptogenic (n=32, 20 %) and NASH (n=21, 13 %). Mean CTP=12.3±1.47 and median MELD=22.7 (range=16-28). SBP was associated with hepatic encephalopathy in 93 (57.7 %), variceal bleed 16 (9.9 %), septic shock in 60 (37.2 %) requiring ventilator support in 47 (29.2 %) with median hospital stay of 7 (range 4-14) days with a high mortality (n=43, 26.7 %) and major causes were being sepsis (83.7 %), variceal bleed (11.7 %) and 2 patients (4.6 %) due to intracranial bleed. The predictors of survival were presence of HE, Child-C status, MELD >24, reduction in ascitic fluid neutrophil count after 48 hr by 13 %, low ascitic fluid glucose <92 mg/dL %, culture positivity for ascetic fluid (p<0.05).

Conclusions:The clinical presentation, advanced liver disease, ascitic fluid low glucose with culture positivity at the baseline and neutrophil count reduction but not the base line ascitic fluid TLC or reduction at 48 hr predict the resolution of SBP and overall outcome.

LO-16

Spontaneous bacterial pleuritis-Clinical characterstics and predictors of outcome in cirrhotic patients

Amrish Sahney, Cyriac Philips Abbey, Chithranshu Vashishth, Shiv Kumar Sarin

Department of Hepatology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Background: Spontaneous bacterial pleuritis (SBPL) is defined as spontaneous infection of a pre-existing hepatic hydrothorax. Studies focusing on natural history, predictors of development and outcome of SBPL are limited.

Aims: Clinical characteristics, bacteriology, and outcome predictors of cirrhotic patients with SBPL.

Patients and Methods: Retrospective analysis of SBPL in cirrhotic patients in a hepatology and liver transplant center. SBPL was defined in cirrhotics as pleural fluid infection fulfilling all the following three criterias a) serum-pleural albumin gradient >1.1 g/dL, b) polymorphonuclear (PMN) leukocyte count >500/mm3 or positive fluid culture with PMN cell count >250 cells/mm3 patients and c) absence of pneumonia or a contiguous infection process on chest radiography. Patients with SBPL (Gp A) were compared with those without (Gp B).

Results: Of the 2,800 cirrhotic patients, 234 (8.4 %) had pleural effusion and 184 (6.5 %) had hepatic hydrothorax. 97.8 % patients with hepatic hydrothorax had ascites. SBPL was diagnosed in 28 (15.2 %) patients with hepatic hydrothorax (Gr. A). Forty percent patients in Gp A and 20 % patients in Gp B received antibiotics for different reasons in last 3 months. These patients were significantly younger (mean age, 43.86±11.72 yr. vs. 49.52±11.65), (p=0.019.) and had higher CTP score (12.83±1.56 vs. 10.1±1.86, p=0.016) than non-SBPL (Gp B) patients. Fifty-seven percent patients in Gp A and 17 % in Gp B had spontaneous bacterial peritonitis (SBP) (p<0.001) and 60 % had hepatic encephalopathy (HE) in Gp A vs. only 25 % in Gp B (p<0.001). E. coli (80 %) and Klebsiella pneumonia (20 %) were the predominant bacteria isolated from the pleural aspirate. In Gp A 7 (24 %) patients died at 1 month compared to 16 deaths (10.25 %) in Gp B (p=.031). Survival at 3 months was also significantly different in two groups (35 % in Gp A vs. 62 % in Gp B). Advanced cirrhosis (CTP ≥12), low serum total protein (≤5.8 g/dL), pleural fluid protein (≤1.7 g/dL) and presence of SBP were associated development of SBPL. On multivariate analysis presence of SBP, HE and antibiotic usage in last 3 months were significantly associated with mortality in Gp A patients.

Conclusion: SBPL is associated with advanced cirrhosis and is significantly associated with SBP. SBPL is a significant cause of mortality in cirrhotic patients presenting as pleural effusion. Advanced cirrhosis, SBP, low pleural fluid and serum total protein are predictors of SBPL development. Presence of SBP, HE and prior antibiotic usage are predictors of short-term mortality in SBPL patients.

LO-17

Bone marrow predicts liver regenerative response to growth factors in decompensated cirrhotics

Lovkesh Anand 1 , K Chandan 1 , Chhagan Bihari 2 , Anupam Kumar 3 , Dhananjay Mathur 3 , Sheetal Rooge 3 , Rakhi Maiwall 1 , Shiv Kumar Sarin 1

1Departments of Hepatology, 2Pathology and 3Research, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Background: Mobilization of bone marrow (BM) cells using growth factors increases regenerative capacity of liver leading to clinical, biochemical and histological improvement in cirrhotics. However, not all patients respond. We investigated parameters in the baseline BM that could help predict responsiveness to therapy.

Methods: After informed consent, thirty consecutive Child's B cirrhotics underwent baseline transjugular liver biopsy (TJLB) and BM examination, treated with either G-CSF 5¼ g/kg or G-CSF 5¼ g/kg + EPO 500 IU/kg for 2 months and TJLB repeated at treatment completion. Markers of liver regeneration were studied in responders (reduction in CTP score >1) and nonresponders.

Results: The CTP score in responders (Gr A, n=16) decreased from 8.7±1.5 to 7.6±1.5 (p-0.003) and increased from 8.8±1.2 to 9.3±1.6 (p- 0.21) in nonresponders. As shown in Fig. 1, in Gr A, αSMA reduced from 2.27±0.59 to 1.13±0.51 (p<0.001), median CD34+ cells increased from 15 to 40 (p=0.001), CD163+cells increased from 2.13±0.6 to 2.6±0.91 (p=0.02) and median Ki67 expression increased from 3 % to 12 % (p=0.006). Baseline BM showed higher number of osteoblast count (p=0.009), CD34 positive hematopoietic stem cells (HSC) (p<0.001), reduced vascularity (p-0.001) and reduced perivascular fibrosis (p=0.04) in responders (group A). FACS analysis of BM aspirate showed higher levels of HSCs (p=0.001), multipotential progenitor cells (p=0.007) and common myeloid progenitors (p=0.004) in Gr A compared to B.

Conclusion: Administration of growth factors leads to liver regeneration by enhancing the cross talk between liver and BM as shown by improved regenerative response in responders. Baseline BM study is very helpful to identify responders prior to liver regenerative therapy.

LO-18

Prevalence, natural history and outcome of overlap syndrome versus autoimmune hepatitis in the Indian continent

Lovkesh Anand , Abby Philips, Varsha Shastry, Shiv Kumar Sarin

Department of Hepatology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Methods: Patients admitted to our hospital in past 4 years were reviewed retrospectively. The diagnosis was confirmed using simplified AIH score and Paris criteria for AIH and OS respectively.

Results: Of the 7,686 patients analyzed, 254 (3.3 %) patients were found to fulfil criteria for AIH and OS-174 (68.5 %) were AIH and 80 (31.5 %) were OS. Patients with OS were older (46 y vs. 42 y, p =0.48) and had higher bilirubin levels (median 3.4 g/dL, IQR 1.8-11.8) as compared to AIH (2.2 g/dL; 1.2-5.9). Standard autoimmune markers were comparable, though, atypical autoimmune marker such as p-ANCA was seen more in OS (10.1 %, n=8). Osteopenia, as measured by DEXA, was more severe in OS patients (21.7 %, n=13), p=0.01. Liver stiffness (FibroscanR) was higher in patients with OS (median 28.4; IQR 17.3-43). Patients of OS predominantly presented with cirrhosis as compared to AIH (72.5% vs. 64.9%; p=0.08). Overall, patients with OS carried poorer prognosis (8.8 % died vs. 5.2 % of AIH; p=0.18). Presence of ASMA in the titre of 1:40 or 1:20 was associated with higher incidence of decompensation among patient in both the groups (p=0.04).

Conclusions: AIH and OS are not uncommon as chronic liver disease in the Indian continent. Patients with OS are older and present more often as cirrhosis and with a poor prognosis. We propose that high suspicion in diagnosis and lower threshold in performing liver biopsy in seemingly non-classical AIH would yield early diagnosis and could improve survival benefit in this group.

LO-19

Prevalence of risk factors for nonalcoholic fatty liver disease in Indian patients with cryptogenic cirrhosis

C Bharath Kumar , Deepu David, Ashish Goel, Jeyamani Ramachandran, Uday Zachariah, K G Sajith, C E Eapen

Department of Hepatology, Christian Medical College, Vellore 632 004, India

Background: Nonalcoholic fatty liver disease (NAFLD) is recognized as an important cause of cirrhosis. Due to difficulty in obtaining and interpreting liver biopsy in cirrhotics, most are labeled as cryptogenic cirrhosis.

Aim: Aim was to study the prevalence of risk factors for NAFLD in cryptogenic cirrhosis.

Methods: During August 2013 to July 2014 all cases (cryptogenic cirrhosis) and controls (hepatitis B/C related cirrhosis) above 40 years of age were consecutively and prospectively recruited. After informed consent, cases and controls underwent a detailed clinical and laboratory evaluation to assess the cause and severity of liver disease and risk factors for NAFLD i.e. DM, obesity and metabolic syndrome.

Results: Forty cases (M-31; age 53±9 years mean±SD; Childs class A/B/C-17/14/9) and 32 controls (M-28; age 54±7 years mean±SD; Childs class A/B/C-16/9/7) were enrolled. The BMI in cases and controls was similar (25 % vs. 24 %, p-0.65). Twenty-two (55 %) cases were obese compared to 14 (43 %) controls as per Asian definition of BMI >25 kg/m2, (p-0.34). Duration of obesity was longer in cases (5±6 years; mean±SD) as compared to controls (3±5 years; mean±SD; p-0.15). DM was more prevalent in cases as compared to controls {18(45 %) vs. 7 (21 %) (p-0.041)}. Eleven (28 %) cases and 4 (13 %) controls had a family history of either DM or obesity. Metabolic syndrome was noted in 29 (72 %) cases compared to 11 (34 %) of controls (p-0.001).

Conclusion: Higher prevalence of risk factors for NAFLD underlies the important contribution of NAFLD in Indian patients with cryptogenic cirrhosis.

LO-20

Body composition analysis among early versus advanced nonalcoholic fatty liver disease patients

R Devaraja , P Madumita, Manoj Kumar Sharma, S K Sarin

Department of Hepatology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Aims: To study body composition pattern in nonalcoholic fatty liver disease (NAFLD) patients and in compensated chronic liver disease patients.

Patients and Methods: Retrospective analysis of NAFLD patients in Hepatology Department. Parameters of body composition as fat mass, total body water, muscle mass, bone mass (kgs), basal metabolic rate, trunk fat mass and bio impedance (Ohm), phase angle were studied using a Tanita• analyser. NAFLD and chronic liver disease were diagnosed based on USG abdomen and fibroScan values.

Results: A total of 200 patients were included: 69 % were male, mean age of 47. 30. 57 % had NAFLD; 43 % had chronic liver disease. Median BMI was 28 kg/m2; median fat percentage of 32. LDL (121.7 vs. 88.75; p< 0.01) and total cholesterol level (186.6 vs. 139.4; p< 0.01) were significantly low. There were no changes in BMI, BMR, impedance and total body water content. Advanced NAFLD patient continued to have high total body fat (31.11 % vs. 34.35 %; p<0.001) and trunk fat (33.40 % vs. 37.80 %; p< 0.05) content. The phase angle was significantly low in advanced NAFLD patient compared to early stage NAFLD (5.23 vs. 5.99; p<0.01).

Conclusion: Body composition analysis showed maintained body weight and fat content even after progression from fatty liver to chronic liver disease stage. However, there was a significant decrease in serum cholesterol level in advanced NAFLD patient compared to early NAFLD stage. Phase angel may be used for assessment of progression of liver disease in NAFLD patients.

LO-21

A prospective open label randomized noninferiority trial to compare the efficacy and safety of monotherapy with noradrenaline and terlipressin in patients of cirrhosis with septic shock admitted to the Intensive care unit (NCT01836224)

Ashok Choudhury , Chitranshu Vasistha, Deepak Saini, Sachin Kumar, K N Chanadn, Rakhi Maiwall, Ajeet Bhadoria, Shiv K Sarin

Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: Cirrhosis and septic shock had changes in the hemodynamics and microcirculation and terlipressin has advantages of improving microcirculation, hepatorenal syndrome and likely prevention of variceal bleed when used as a vasopressor in addition to supplementing relative vasopressin deficiency. The present study is to compare the efficacy and safety of monotherapy with noradrenaline or terlipressin in patients of cirrhosis with septic shock.

Methods: Within 30 minutes of presentation, consecutive patients of decompensated cirrhosis with septic shock were randomized in an open label manner to receive either continuous infusion of terlipressin (Group-A, 1.3-5,2 mcg/min, n=38) or noradrenaline (Group-B, at 7.5-60 mcg/min, n=40) with the aim to achieve a target mean arterial pressure (MAP) of >65 mmHg. The standard medical care was equal in both the groups. Monitoring for perfusion, metabolic parameters and hemodynamics were recorded and followed from admission till death or 28 days follow up.

Results: Seventy-eight patients (Group A-38, Group B-40) matched for age, sex and etiology of cirrhosis with median CTP (12.5 vs. 13, p=0.25), MELD (34 vs. 34, p=0.63) and SOFA score (13 vs. 15, p=0.42). At admission, the major source of sepsis were spontaneous bacterial peritonitis (SBP) followed by pneumonia, but the second hit sepsis was predominantly due to pneumonia (93 % vs. 64.7 %, p=0.12) with no SBP in terlipressin group (0 % vs. 23.5 % p<0.05). The target MAP at 6 hours was achieved in both the groups (91 % vs. 80 % p=0.18). Use of terlipressin compared to noradrenaline was associated with lower failure rate (25 %, 62.5 %, p <0.05), better maintenance of MAP (93.8 % vs. 72.5 %, p=0.02) with cessation of vasopressor requirement (50 % vs. 25 % p=0.03) at 48 hours, improved urine output at 24 hours (59 % vs. 36 %, p=0.05) and no variceal bleed (0 % vs. 15.45 %, p=0.03) without significantly increased adverse effects (40.6 % vs. 22.5 %, p=0.12). Terlipressin use showed delayed resolution of acute kidney injury on fifth day (59.4 % vs. 16.75, p=0.08) with improved lactate clearance, central venus oxygen saturation and CO2 gradient in venous – arterial blood gases (p=NS). An early survival advantage was seen with the use of terlipressin (93.5 % vs. 75 %, p=0.02) in the first 48 hours, but not at 28 days.

Conclusion: Terlipressin as a vasopressor is non-inferior to noradrenaline with greater hemodynamic stability, early survival benefit, improved urine output, reduced variceal bleed and decreased incidence of nosocomial SBP with nonfatal and reversible adverse effects. Its use is recommended in decompensated cirrhotics presenting with septic shock.

LO-22

Alternatively activated M2 macrophages promotes hepatocyte differentiation in hepatic progenitor cell mediated liver regeneration in acute-on-chronic liver failure patients

Dhananjay Kumar 1 , Sheetalnath Rooge 1 , Smriti Shubham 1 , Adil Bhat 1 , Charvi Syal 1 , Archana Rastogi 3 , Chagan Bihari 3 , Viniyendra Pamecha 4 , Anupam Kumar 1 , Shiv K Sarin 2

1Department of Research, 2Hepatology, 3 Pathology, and 4HPB Surgery, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Macrophages play myriad roles in liver degeneration and regeneration. The changing microenvironment of different setting of liver disease affects the polarization of macrophage and how different subtypes affects hepatic regeneration remains unclear.

Aim: To understand the effect of liver microenvironment on the plasticity of liver macrophage and their role in regeneration.

Methodology: M1/M2 macrophage marker genes expression by using qRT-PCR in biopsy/explants in ACLF, ALF, CLD. Ki67, CK-19 staining for the nature of liver regeneration. CD68 (tissue macrophages) CD163 (M2 macrophages) for analysis of macrophages in liver tissue from patients with ACLF, ALF, and CLD (n=15, 21 and 22). Expression of CD68, CD163 were correlated with hepatocyte self-replication, HPC activation and maturation.

Results: qRT-PCR result show increase in M2 gene markers CD163, CD206 &TGM2 and decrease in M1 markers iNOS, CD80 in ACLF comparison to CLD and increase in M2 gene markers CD163, CD206 and TGM2) and decrease in M1 markers in iNOS and CD80 in ACLF comparison to ALF. IHC analysis shows increase in Ki67+ hepatocytes in ALF vs. ACLF. Further, the number of CK19+ HPC and its maturational lineages was increased in ACLF than ALF and CLD. Spearman correlation showed CD163 positivity and M2/M1 ratio is associated with HPC differentiation to hepatocyte. PCR analysis of PU.1 and Myb suggest that increase in PU.1 expression in ACLF in comparison to ALF and CLD suggesting that major population of M2 in ACLF are kupffer cells.

Conclusions: M2 are the major population in ACLF which are Kupffer cell origin and promotes differentiation of HPC to hepatocyte.

LO-23

Systemic inflammatory response syndrome - A potential clinical marker for early sepsis and survival in acute-on-chronic liver failure

Ashok Kumar Choudhury , Chitranshu Vashistha, Tanmay Vyas, K N Chandan, Rakhi Maiwal, Ajeet Bhadoria, Shiv K Sarin

Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Background and Aims: Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation. We investigated the clinical profile, dynamicity, predictors, natural history and outcome in hospitalized acute-on-chronic liver failure (ACLF) cohort.

Methods: Consecutive patients of ACLF were evaluated for components of SIRS, development of sepsis and associated complications till liver transplant, 90 days follow up or death with periodic sepsis screening for initial 15 days followed by ‘on suspicion’ screening.

Results: All (n=561) ACLF patients underwent sepsis screening at admission. Three hundred and sixty (64.2 %) patients had ≥2 components of SIRS; median age 42 years (IQR 35-54), 88 % male majority being alcoholic hepatitis (55 %) with mean CTP score 12.09 ±1.48 and median MELD 29.6, IOR=24.4-37.6. At baseline, 33 % and 4.5 % patients had sepsis and septic shock respectively. At day 4 (D4), new onset SIRS in 55.4 % and resolution of SIRS seen in 44.7 % cases. Persistence of SIRS at D4 (85.2 vs. 50.7 %, p=0.05) or D7 (6.4 % vs. 39.5 %, p=0.05), ≥2 organ failure (CLIF SOFA score) were associated with high mortality and correlate with persistence SIRS (p<0.05). Number of organ failure increases with increasing number of SIRS components (<2 vs. ≥2, 39 % vs. 73 %, p=0.01). Persistent hyperlactemia (median=2.1 vs. 1.5 mmoL/lit) at D4 was independent predictor of mortality (OR=4, 95 % CI 1.6-9.6). Serum procalcitonin >0.5 ng/mL was associated with SIRS (p=0.05). The mortality was higher in presence of SIRS at baseline irrespective of sepsis compared to those without SIRS (p<0.05).

Conclusion: SIRS is an important predictor of early sepsis, organ failure, survival in ACLF. Onset of SIRS may be a clue for early or occult sepsis and prompt use of prophylactic antibiotics is highly recommended.

Baseline parameters

Mortality %

p value

Overall in ACLF cohort

61.6

<0.05

No SIRS at baseline

48.7

<0.05

SIRS at baseline

82.1

<0.05

Sepsis at baseline

82.2

NS

Presence of SIRS irrespective of sepsis associated with high mortality compared to those have no SIRS (p<0.05). Overall mortality in SIRS or sepsis is equal

LO-24

Prevalence of duodenal ulcer in patients with chronic liver disease

N A Rajesh , Kani Sheik Mohd, Ratnakar Kini, K Premkumar, T Pugzahendhi, Mohd Ali

Department of Gastroenterology, Madras Medical College, Chennai 600 003, India

Introduction: No data is available regarding frequency of DU among cirrhotics in our community, consequently diagnosis of DU may be missed and appropriate management may be delayed.

Aim of the Study: To study the prevalence of duodenal ulcer in patients with CLD.

Material and Methods: Prospective study of 100 patients with CLD who underwent OGD for various indications at Madras Medical College.

Results: Eighty-eight percent of patients had esophageal varices, 25 % had gastric varices, 65 % had PZHTG, 21 % had DU, 5 % had antral ulcers. Twenty-eight percent of patients who had DU were asymptomatic, 45 % had complaints of epigastric pain, 24 % had UGI bleed. In our study 56 % of UGI bleed in cirrhosis was due to variceal rupture, 25 % of bleed was due to PHTG, 16 % of bleed was due to DU and 3 % of bleed was due to GAVE.

Discussion: The prevalence of DU was higher and statistically significant with p value

LO-25

Liver histomorphological spectrum in drug induced liver injury

Archana Rastogi 1 , Chhagan Bihari 1 , Shiv Kumar Sarin 2

1Departments of Pathology and 2Hepatology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Background: Drug induced liver injury (DILI) is an important but poorly understood cause of acute and chronic liver diseases (CLD). Liver biopsy, an important diagnostic test for DILI, provides valuable information about the diagnosis, severity, mechanism and prognosis.

Aim: To analyze various liver histomorphological patterns of DILI method: 4,500 liver biopsies received over a period of 4 years were reviewed. The purpose of biopsies were: to confirm DILI, to assess the extent of liver damage, to exclude coexistent DILI in cases with underlying CLD and an important group which showed unusual histomorphology that was compatible with DILI.

Results: Fifty-nine (1.5 %) of the total liver biopsies, had features consistent with DILI. Median age of the patients was 39 years and male:female ratio 1.3:1. Patterns seen: hepatitic (16 %), cholestatic (20 %), mixed hepatitic-cholestatic (27 %), steatosis/steatohepatitis (16 %), vascular (4 %) and granulomatous (11 %) and others (6 %). Commonest pattern was mixed cholestatic-hepatitic. Thirty-two percent of the acute liver failure were attributable to anti-tubercular therapy. Drugs implicated in liver injury were Ayurvedic medicines, health supplements, anti-tubercular therapy, antibiotics, anti-metabolites, anti-diabetic, anti-arrhythmic, anti-neoplastic drugs, interferon and steroids. Commonest agents implicated in these cases were herbal medicines, health supplements and anti-tubercular therapy.

Conclusion: DILI presents with varied histomorphological patterns, therefore should always be considered with the more common etiological conditions. Histomorphology and patterns in liver biopsy provide clues in unsuspected cases and may point to particular group of drugs as causative agent.

LO-26

Etiological profile of hepatocellular carcinoma in a tertiary care centre in Kerala

Aby Somu , Mathew Philip, Joseph John, G N Ramesh, Prakash Zacharias

P V S Memorial Hospital, Kaloor, Ernakulam, Cochin 682 017, India

Background: Primary liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. The etiology and prevalence of hepatocellular carcinoma (HCC) is different in various geographic regions. India falls in the low incidence zone. There is paucity of data from India regarding HCC.

Aim: The aim of the study: To study the etiological profile of HCC.

Methods: Data analysis of HCC patients enrolled in liver clinic between February 2013 and August 2014.

Results: Total number of HCC cases were 180 - males 165 (91.7 %), females 15 (8.3 %). Mean age at diagnosis was 60.6 years. The etiology of HCC was: alcohol 127 (70.5 %), cryptogenic 25 (13.9 %), hepatitis B 17 (9.4 %), hepatitis C 11 (6.1 %) and multiple causes in 10 (5.5 %). Sixty (33.3 %) patients were chronic smokers. Diabetes was associated with HCC in 107 (59.4 %) patients. Serum AFP was >200 ng/mL in 60 patients (33.3 %). Portal vein invasion was seen at diagnosis in 68 patients (37.8 %). Disseminated disease was seen in 7 patients (3.9 %). Tissue diagnosis was needed in 17 patients.

Conclusion: The risk of HCC is increased in chronic liver disease. The etiological profile of HCC in South India is different from the Western and north Indian population. Ethanol is the most common cause of HCC with diabetes a significant cofactor.

LO-27

Awareness of liver diseases in community

Krishnadas Devadas, A S Asif , Anish Philip, **o Thomas, R Sobhanadevi

Government Medical College, Kottayam 686 008, India

Treating physicians we all are aware of the fact that knowledge and behavioral modifications play an important role in the prevention and, treatment of liver diseases. Recent community based studies are lacking in this aspect.

Aims: 1. To assess the knowledge about, and attitude towards liver diseases in people belonging to various sections in our community on the occasion of World Hepatitis day. 2. To conduct further long-term studies and appropriate steps to improve the scenario.

Methods: An interview was performed among 1st and 2nd professional MBBS students, Nursing students, Pharmacy students, arts and science college students, patients with and without liver disease and laymen. Gross marks obtained after the interview, and individual marks for various questions were analyzed under various headings. The questions were based on major causes of liver disease like ALD, viral hepatitis, NAFLD, DILI, and organ transplantation.

Results: Overall 1,606 subjects were interviewed of which majority were females (59.2 %). Females outnumbered males in all groups except CLD group. Females had significantly (p<.05) better marks compared to males under almost all headings. On assessment it was found that alchohol related liver disease was one which is familiar to all the categories. But response to the liver proprietary medicines revealed the influence of their advertisements. Another fact noted during study was the lack of enough knowledge about viral hepatitis, indigenous medicines, DILI and NAFLD.

Conclusions: Further community based studies and interventions are required to enhance the awareness about various liver diseases and promotion of healthy practices.

LO-28

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LO-29

WITHDRAWN

LO-30

Clinical profile of bacterial infections in decompensated cirrhosis

G Paul Cheruvathur , P V Mashhood, George Peter, Tony, A B Suthanu, K S Prashanth, N Premalatha, K R V Kumar

Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram 695 011, India

Background: Bacterial infections are a major cause for hospital admissions and mortality in patients with decompensated cirrhosis. Patients with decompensated cirrhosis are more prone to infections than patients with compensated cirrhosis. The severity of the infections increases with advanced stages of liver disease.

Aim: To study the clinical profile of bacterial infections in patients admitted with decompensated cirrhosis.

Methods: The retrospective study included patients with decompensated cirrhosis liver and bacterial infections admitted to our department. The diagnosis of liver cirrhosis was based on medical history, physical examination, biochemical parameters, ultrasound findings and/or liver biopsy and bacterial infections were diagnosed using clinical features and lab parameters including cultures and gram stain. Severity of liver disease was assessed using CTP and MELD scores.

Results: There were a total of 346 cirrhotic patients admitted with various bacterial infections during the study period. The mean age was 59±11 years, males constituted 68 %. Alcohol was the most common etiology of cirrhosis 62 %. The mean MELD score of the patients were 17.2±4.1 and mean CTP score was 9.3±2.2. The most common infection encountered was SBP 43 % followed by cellulitis 31 %, urinary tract infection 23 %, pneumonia 16 %, cholangitis 8 %, gastroenteritis 4 %, perianal abscess 3 % and necrotizing fascitis was diagnosed in 2 patients. Multiple sites of infection were identified in 21 % of patients. Culture positivity was detected in 38 %. Most common organism isolated in culture was E coli other organisms were klebsiella, pseudomonas, S aeurus, MRSA and Acinitobacter. Acute kidney injury (AKI) was detected in 34 % of patients. Overall mortality was 31 %.

Conclusions: Most common infection leading to admission was SBP and most prevalent organism isolated was E coli. Incidence of AKI was high in these patients. Over a third of the patients admitted with infections succumbed to their illness.

LO-31

Serum procalcitonin predicts spontaneous bacterial peritonitis in patients with cirrhosis

K S Prasanna , K G Sajith, U G Zachariah, A Goel, C E Eapen

Department of Hepatology, Christian Medical College, Vellore 632 004, India

Background: Procalcitonin (PCT), a peptide precursor of calcitonin, is a marker of sepsis. We aimed to study the role of serum procalcitonin in predicting spontaneous bacterial peritonitis (SBP) in cirrhotic patients.

Patients and Methods: It was a retrospective chart review of consecutive patients with chronic liver disease (CLD) diagnosed on the basis of clinical, biochemical and radiological parameters. Patients with suspected infection were included.

Results: Eighty-eight patients [age 45±13.6 yrs (mean±SD), M:62, CTP-A/B/C :17/18/51, MELD (21±9.21)] were included in this study. Twenty-seven (31.3 %) patients had SBP. On univariate analysis, age, serum albumin, MELD score (24.5±8.4 vs. 19.7±9.2; p 0.027) and procalcitonin [2.33(0.17-25.39) ng/mL vs. 0.622 (0.045-27.08) ng/mL; p <0.0001] levels were significantly different in those with SBP in comparison to those without SBP. On multivariate analysis, adjusting for MELD, age and serum albumin, PCT remained an independent predictor of SBP in patients with cirrhosis (p: 0.002). On ROC analysis a serum procalcitonin value of 0.84 ng/mL had a sensitivity of 82 % and a specificity of 57 % in predicting SBP. Presence of SBP significantly predicted in-hospital mortality (14/27 vs. 15/59; p: 0.026). However, serum PCT at admission, was not useful in predicting mortality (p: 0.701) in patients with cirrhosis.

Conclusion: Elevated serum procalcitonin was a significant independent predictor of SBP. Serum procalcitonin value of 0.84 ng/mL has a good sensitivity as a predictor of SBP in patients with CLD.

LO-32

microRNA-194 regulates the expression of TNF-α, IL-1α and IL-6 via modulating akt/NF-κB pathway in hepatic stellate cells

Parul Gupta , Satendra Kumar, Kishore Pant, Pushpendra Kumar Sahu, Senthil Kumar Venugopal

Faculty of Life Sciences and Biotechnology, South Asian University, Akbar Bhawan, Chanakyapuri, New Delhi 110 021, India

Background: Hepatic stellate cells are the key cells involved in the progression of liver fibrosis. Under normal physiological conditions, these cells are quiescent and store vitamin A granules. In response to injury, these cells proliferate, secrete extracellular matrix proteins and transdifferentiate into myofibroblast like cells. Previously we had shown that miRNA-194 was inhibited in fibrosis and its overexpression led to decreased rac1 protein levels. In this study, we hypothesized that miRNA-194 could inhibit fibrosis via akt/NF-κB-induced profibrogenic cytokines secretion pathway.

Methods: microRNA-194 was over-expressed in LX-2 cells. Total RNA enriched with miRNAs was isolated, cDNA was synthesized and real time PCR for miRNA-194 or the pro-inflammatory cytokines (IL-1α, IL-6 and TNF-α) was performed. Total cellular protein was isolated and Western blots were performed for Akt, phospho-akt, NF-kB p65 subunit and fibrosin. Both cell proliferation and apoptotic assays, using titer-glo and TUNEL assay, were performed in microRNA-194 transfected cells.

Results: Over-expression of miRNA-194 led to 20-fold increase of intracellular levels of miRNA-194 as determined by real time RT-PCR. Transfection of miRNA-194 in LX-2 cells resulted in a significant decrease in the expression of IL-1α, (55 % inhibition), IL-6 (30 % inhibition) and TNF-α (35 % inhibition) compared to NS-miRNA transfected cells. Western blot results showed decreased akt activation (8-fold decrease), NF-kB p65 levels (6-fold decrease) and fibrosin levels (2-fold decrease) compared to NS-miRNA transfected cells. Over-expression of miRNA-194 resulted in a significant decrease in proliferation while no effect was observed on apoptosis in LX-2 cells. Intracellular expression of miRNA-194 was inhibited (2-4 fold decreased compared to the control cells) in response to these pro-fibrogenic cytokines.

Conclusion: These data demonstrate that over-expression of miRNA-194 could inhibit fibrogenesis, at least in part, by inhibiting profibrogenic cytokines via p-akt/akt/NF-kB pathway in hepatic stellate cells.

LO-33

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LO-34

Prevalence of occult hepatitis B infection and risk factors of NAFLD in non-B non-C hepatocellular carcinoma

Deepu David, Jeyamani Ramachandran, Priya Abraham, Banumathi Ramakrishna, Philip Joseph, Ashish Goel, C E Eapen

Christian Medical College Hospital, Vellore 632 004, India

Background and Aims: Studies elsewhere have found high prevalence of occult hepatitis B infection (OBI) and risk factors of nonalcoholic fatty liver disease (NAFLD) in patients with non-B non-C hepatocellular carcinoma (HCC). In this study, we aimed to analyze the prevalence of risk factors of NAFLD and OBI.

Methods: Patients with HCC, negative for HBsAg and anti-HCV antibody were included. Besides clinical examination, anthropometric measures and routine laboratory investigations, patients underwent testing for antibody against hepatitis B core antigen (anti-HBc) and quantitative PCR for hepatitis B virus DNA (HBV DNA). OBI was defined as presence of HBV DNA in the absence of HBsAg positivity. All patients were assessed for risk factors of NAFLD such as diabetes (DM), hypertension, dyslipidemia, metabolic syndrome (MS), waist hip ratio and family history of DM.

Results: During April 2013 to July 2014, 43 patients of HCC (M:35; age: 59±10 years; mean, SD) were included. At presentation, 11 (26 %) patients were within Milan criteria and MELD score was 11±4.23 patients were in Child’s class A, 15 in B and 5 in C. Ten (23 %) patients had significant alcohol intake (>20 gm/d for atleast 5 years). Twelve (28 %) were positive for anti-HBc. However, no one had detectable HBV DNA. Prevalence of risk factors for NAFLD was DM: 22 (51 %), hypertension: 15 (34 %), dyslipidemia: 12 (28 %) and MS: 20 (47 %). Average BMI in patients without ascites was 24±4 kg/m2. Thirty-eight (88 %) had at least one risk factor for NAFLD.

Conclusion: NAFLD, but not OBI, predisposes to hitherto unexplained HCC in India.

LO-35

A prospective study to compare inhibitory control test to a psychometric hepatic encephalopathy score to diagnose minimal hepatic encephalopathy in patients of cirrhosis

Dhaval Gupta , Jatin Patel, Dattatrey Solanke, Meghraj Ingle, Prabha Sawant

Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and Lokmanya Tilak Municipal General Hospital, Sion, Mumbai 400 022, India

Background and Aims: Minimal hepatic encephalopathy (MHE) is mild cognitive impairment in cirrhotics and requires specialized tests for diagnosis.

Aims: Aims were to determine usefulness of inhibitory control test (ICT) for diagnosis of MHE in Indian subcontinent, to correlate it with severity of liver disease and to determine its prognostic significance.

Methods: Study conducted at large tertiary care center in Mumbai. Two hundred patients with cirrhosis and 200 healthy controls enrolled. Only patients were subjected to psychometric hepatic encephalopathy score (PHES). While patients and controls both subjected to ICT. Forty subjects underwent ICT twice.

Results: MHE was diagnosed when PHES was ≤-5. ICT considered abnormal when numbers of ICT lures were ≥14. Total 135 (67.5 %) patients had MHE. ICT lures were higher in MHE as compared to those without MHE in cirrhotics [17.27(95 % CI (13.9-22.3) vs. 8.79 (95 % CI (6.8-12.60) p<.001]. Target accuracy was lower in MHE as compared without MHE [84.35(95 % CI (78.5-89.8) vs. 95.36 (95 % CI (90.1-99.2) p<.001]. ICT had 92.6 % sensitivity and 78.5 % specificity with area under curve value 0.855 (95 % CI=0.791-0.920) for MHE diagnosis. ICT correlated with Child (CTP) class (p<.001) and model for end-stage liver disease (MELD) score (p<.001) and predicted development of overt hepatic encephalopathy (OHE) and probable survival with excellent test retest reliability.

Conclusion: ICT is useful for diagnosis of MHE in patients with cirrhosis in Indian population. It correlates with disease severity and predicts development of development of OHE and probable survival with excellent test-retest reliability.

LO-36

Comparison of four model for end-stage liver disease: Based prognostic systems for cirrhosis

Jatin Patel , Dhaval Gupta, Nirav Pipaliya, Meghraj Ingle, Prabha Sawant

Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and Lokmanya Tilak Municipal General Hospital, Sion, Mumbai 400 022, India

Aim: To investigate the prognostic value of the model for end-stage liver disease (MELD), the MELD with incorporation of serum sodium (MELD-Na), the MELD to sodium (MESO) index and the integrated MELD (iMELD) for prediction of mortality in decompensated cirrhosis.

Methods: Prospectively 365 patients with decompensated cirrhosis were enrolled. MELD, MELD-Na, MESO and iMELD scores were calculated on admission. All patients were followed up at least 1 year. The predictive prognosis related with the four models was determined by the area under the receiver operating characteristic curve (AUC) of the four parameters.

Results: At 3, 6 and 12 months patients who died has higher mean MELD, MELD-na, MESO and iMELD scores than survivors. At 3 months of enrollment, the MELD-Na and iMELD had the higher AUC (0.859 and 0.844 respectively) and was followed by the MESO (0.835) and MELD (0.824). For predicting 6 months mortality iMELD had highest AUC (0.895) followed by MELD-Na (0.894), MESO (0.880) and MELD (0.873). At 12 months iMELD still had highest AUC (0.906) followed by MELD-Na (0.894), MESO (0.870) and MELD (0.862).

Conclusion: MELD-Na, iMELD and MESO can all exactly predict the prognosis of patients with decompensated cirrhosis for short and intermediate period, and may enhance the prognostic accuracy of MELD. The iMELD is better prognostic model for outcome prediction in patients with decompensated cirrhosis.

LO-37

Clinical study of liver abscess with current trend in etiology and management

Kaivan Shah , Mallangaud Patil, Meghraj Ingle, Aniruddha Phadake, Prabha Sawant

Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and Lokmanya Tilak Municipal General Hospital, Sion, Mumbai 400 022, India

Material and Methods: This was prospective single Centre observational study. One hundred and two patients admitted and attending OPD of Department of Gastroenterology, Lokmanya Tilak Medical College with liver abscess were enrolled in study. All patients underwent routine blood and IgG ELISA E. histolytica and ultrasonography. Aspiration of liver abscess was done according to current standard guidelines under radiological guidance with strict aseptic precautions in Radiology Department.

Results: Out of 102, 78 (76.5 %) had amebic liver abscess (ALA) 24 (23.5 %) had pyogenic liver abscess (PLA) and 9.8 % had combine amebic and pyogenic abscess. Twenty-four percent of ALA and 58 % PLA were multiple. 90.2 % patients were male. In ALA M:F 76:2. In PLA M:F 16:8. Most common symptom was abdominal pain 92 % and fever in 88 % chest pain in 14 %. Twenty-three percent of ALA had presiding history of diarrhea 3 weeks before.

Etiology: ALA alcohol 60 % diabetes 14 % and HIV positivity 4 %. PLA diabetes 30 %, post-ERCP cholangitis in 20 %, CBD stone with cholangitis in 12.5 %, CBD stricture with cholangitis in 8 % and past history of appendicular abscess 5 %, postcholecystectomy 5 %. Complications (14 %) with rupture (9.8 %) Budd-Chiari syndrome in 2.9 %. Bile leak 0.9 % death 0.9 %. In ALA 41 % require drainage (pig tailing) and 59 % were managed conservatively with antibiotics. Indication for drainage non-resolving symptoms (50 %), left lobe abscess (37 %), rupture (18 %), subcapsular abscess (3 %), compression of hepatic vein (3 %) and 1.2 % patients with bile leak required ERCP. In pyogenic abscess group all require intervention either drainage (67 %) or ERCP (45 %). All patients were treated with higher antibiotics. Organism identified were E. coli 60 % kleibsiella (25 %) acinetobacter (7.5 %) and enterococcus (7.5 %).

Conclusion: Data of liver abscess in Indian subcontinent are sparse. ALA was the commonest etiology. Atibiotics and pig tailing comprise the main stay of management.

LO-38

WITHDRAWN

LO-39

An mRNA expression study of MGMT, RUNX3 and EZH2 in hepatocellular carcinoma in North East India

Parikhit Borthakur 1 , Kangkana Kataki 1,2 , Snigdha Saikia 1 , Md. Ghaznavi Idris 1 , Anupam Sarma 2 , Manab Deka 1 , Subhash Medhi 1

1Department of Biological Science, Gauhati University, Guwahati, Assam 14, and 2Dr B Borooah Cancer Institute, Gopinath Nagar, Guwahati, 781 016, Assam

Background: Epigenetic modifications are central to many human diseases including cancer. Hepatocellular carcinoma (HCC) is one of the most common cancers in North East India. Our study correlates expression of three epigenetic-prognostic cancer markers, O6-methylguanine DNA methyl-transferase (MGMT), Enhancer of zeste- homolog-2 (EZH2), and Runt-related transcription factor 3 (RUNX3) in HCC.

Method: Blood sample of 40 individuals were included in this study, 20-HCC samples (n=13, HBV-caused n=7, cryptogenic) and 20-healthy controls. Primers for EZH2, RUNX3 and MGMT were designed using NCBI and Primer-3 tool. RT-PCR (Rotor-gene, QAIGEN) was used to determine mRNA-expression profile with Î2-Actin as internal control.

Result: mRNA expression analysis for all the three genes were found to be up-regulated in HCC for both HBV mediated and cryptogenic HCC samples (fold change >1). Fold change for cryptogenic HCC samples were found higher compared to HBV mediated HCC samples.

Conclusion: Above study reveals that MGMT, RUNX3 and EZH2 are up-regulated in our patient groups. Higher expression of EZH2 indicates poor prognosis of the disease. High expression of RUNX3 and MGMT show disconcordance with other studies and may contribute to better prognosis of the disease in our cohort. DNA methylation-based markers for prognosis and diagnosis are still under study and its use in clinical practice has yet to be implemented. Small sample size is a limiting factor in this study which needs further evaluation.

LO-40

Antibiotic prophylaxis for SBP in cirrhosis-A validated preventive measure or an exercise in futility?

B Harshavardhan Rao , I Siyad, G Rajesh, Rama P Venu, M Geetha, V P Bhanu, R Harikumar Nair, Anoop Koshy, Jeffey George, V A Narayanan, V Balakrishnan

Department of Gastroenterology, Amrita Institute of Medical Sciences, AIMS Ponekkara PO, Kochi 682 041, India

Background and Aim of the study: Patients with cirrhosis are at risk of develo** spontaneous bacterial peritonitis, necessitating primary or secondary antibiotic prophylaxis usually with quinolones. However, prolonged use can favor colonisation with resistant organisms thereby reducing the efficacy of antibiotic prophylaxis. This study aimed to investigate the prevalence of ESBL positive organisms in the stool samples of cirrhotic patients.

Material and Methods: This was an observational study where a random sample of 100 patients of liver cirrhosis along with age-matched controls were included and their stool samples were cultured to look for ESBL positive organisms. Statistical analysis was performed using SPSS 14.0.

Results: The mean age was 52.56±10.26 years with a preponderance of males (n=83) which was comparable to the control group. A majority of patients had decompensated liver disease (37 % Child B; 48 % Child C) of which, 59 % had ascites and 43 % of the patients were on antibiotic prophylaxis. The prevalence of ESBL-positive stool samples in cirrhotics was 77 % as opposed to 29 % in the control group (p 0.00) with E. coli accounting for a majority of the ESBL-positive samples (n=57; 74 %). Among the patients not on antibiotic prophylaxis, 71.9 % were positive for ESBL organisms which was also significantly higher than controls (p-0.001).

Conclusions: The prevalence of ESBL positive organisms was significantly higher in patients with cirrhosis of liver as compared to controls indicating the selective colonisation of resistant bacteria indicating the need for an individual-based tailoring of antibiotic therapy in the future.

LO-41

WITHDRAWN

LO-42

Study on correlation of HBsAg quantification with DNA levels in a patients with chronic hepatitis B

Balaji Gurappa , P Ganesh, T S Rajkumar, R Balamurali, G Ramkumar, K Muthukumar

Department of Digestive Health and Diseases, Kilpauk Medical College and Hospital, Chennai 600 010, India

Background: Chronic hepatitis B is a major health problem affecting more than 350 millions globally. HBsAg is the hallmark for the diagnosis of HBV infection. There is paucity of Indian data regarding serum HBsAg quantification levels (qHBsAg) in treatment-nave chronic hepatitis B (CHB). This study was done to determine correlation of qHBsAg with hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels.

Materials and Methods: Prospective, ongoing study. All treatment-nave chronic hepatitis B patients were enrolled in our study. HBsAg quantification was performed using the Architect chemiluminescence system.

Results: Total 142 patients were included so far. Among 21/142 were HBe-positive and 121/142 were HBe-negative patients. Fourteen out of 21 (66.6 %) of e-positive belong to young age group. qHBsAg levels were high and correlates with DNA levels in e-postive group but not correlating with DNA levels in e-negative group. Among e-positive ALT elevation (>ULN) were seen in 71 % which is correlating with high qHBsAg levels (>1000 IU/mL). But in e-negative, ALT elevation were only 25 % despite high qHBsAg levels in most of the patients and high qHBsAg levels does not correlate with ALT.

Conclusion: qHBsAg levels correlates well with DNA levels in HBe-positive. Single point measurement of qHBsAg level could predict the replicative state. High levels also correlates with elevated ALT levels in e-positive state. qHBsAg estimation is cost effective.

LO-43

A study on antitubercular therapy hepatic adaptation and progress to DILI and risk factors for DILI

C Vaishnavi Priyaa , K Muthukumaran, G Ramkumar, R Balamurali, T Rajkumar Solomon, P Ganesh

Department of Digestive Health and Diseases, Government Kilpauk Medical College, Chennai 600 010, India

Aim: To identify antitubercular therapy (ATT) induced liver injury ahead of clinical onset by monitoring lab parameters and identify risk factors for DILI.

Materials and Methods: A single Centre study with 150 eligible patients started on ATT, with pretreatment baseline LFT values. Then LFT was monitored every weekly for first month, fortnightly for next two months and monthly at the end of the therapy.

Results: Twenty-one (14 %) had a transient raise of enzymes 5ULN at end of second week. They were changed over to non DOTS non hepatotoxic SEO regime. One male with low viral load chronic hepatitis B, had raise of 2nd week ALT> 3ULN, persisted three weeks and reverted to baseline. Of two (1.3 %) ACLF (DCLD), one recovered with change of regime while one succumbed at end of first week. One elderly diabetic female succumbed to ALF, where an initial transient raise was missed. 1.3 % died of ALF.

Conclusion: Monitoring LFT with insight into hepatic adaptation, idiosyncrasy, and risk factors detects liver injury ahead of clinical onset and may prevent serious ATT DILI.

LO-44

Hepatic venous outflow tract obstruction: A risk factor for hepatocellular carcinoma?

Shashi Bala Paul, Shalimar, Vishnubhatla Sreenivas, R Shivanand, Gamanagatti, Hanish Sharma, Ekta Dhamija, Subrat Kumar Acharya

Departments of Radiodiagnosis, Gastroenterology, and Biostatistics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 220 029. India

Background: Hepatic venous outflow tract obstruction (HVOTO) is an established cause of cirrhosis. The frequency of hepatocellular carcinoma (HCC) in such patients is unclear.

Methods: The clinical, biochemical, imaging findings and follow up details of 421 HVOTO patients were retrieved from hospital records and two studies were designed to address the above questions. A retrospective cohort study was performed to assess the incidence of HCC and a case control study was conducted to identify the risk factors associated with HCC in HVOTO.

Results: Of the 421 HVOTO patients, 236 (56.1 %) were males, 8 had HCC at presentation (prevalence 1.9 %). Another 8 of remaining 413 developed HCC during 2076.2 person-yearss follow up (mean 5.03±4.65 years, range 0.08 years to 20 years). The cumulative incidence of HCC was 3.47 % (CI: 1.28 -9.2 %) at 10 years. The case control study included 16 HCC patients as cases and the remaining 405 as controls. The mean age (±SD) was 36.2±11.4 years for cases and 29±10.3 years for controls (p<0.009). The factors independently associated with development of HCC included presence of cirrhosis, combined IVC and HV block (OR 5.58) and long segment IVC block (OR 6.5).

Conclusions: HVOTO is a risk factor for develo** HCC. Active surveillance should be undertaken in patients with underlying liver cirrhosis, combined block of IVC and HV and long segment IVC block.

GB-01

Clinical and ERCP profile of biliary stricture in tertiary care hospital

P Laksmana Chandra , P Shravan Kumar, M Umadevi, M Ramanna

Department of Gastroenterology, Gandhi Medical College Hospital, Hyderabad 500 003, India

Background/Aim: Biliary stricture is a common problem in GIT. In this study, we aimed at identifying clinical and etiological profile of biliary stricture in Gandhi Hospital.

Patients and Methods: In a retrospective study, 86 patients of biliary stricture who underwent ERCP over a period of 3 years from 2010-20013 were included. Demographic, clinical, biochemical and ultrasonographic parameters were recorded. Other imaging modalities like CT, MRCP were recorded. ERCP findings were analyzed and biopsy details were noted.

Results: Of the 86 patients 40 males (47 %); median age 42 years; range 35-68 years and 46 females (53 %); median age 40 range 25-55  years. The clinical presentation include jaundice 54 (82 %), abdominal pain 25 (38 %), vomiting 15 (23 %), anorexia 25 (38 %), loss of weight 20 (30 %). The spectrum of diseases diagnosed include : Benign biliary stricture 36 (55 %) causes of which include post cholecystectomy biliary stricture 10 (28 %), chronic pancreatitis with distal CBD stricture 10 (28 %), choledocholithiasis 8 (22 %) primary sclerosing cholangitis 2 (6 %) portal biliopathy 2 (6 %) idiopathic 4 (11 %). Malignant biliary strictures 50 (58 %)- ampullary carcinoma 20 (40 %), hilar cholangiocarcinoma 19 (38 %), distal cholangiocarcinoma 3 (6 %), carcinoma head of pancreas 6 (12 %), carcinoma gallbladder 2 (4 %).

Conclusion: Most common cause of benign biliary stricture found to be associated with postoperative and chronic pancreatitis. Most common malignant cause ampullary and hilar cholangiocarcinoma in this study.

GB-02

Comparision of ultrasound, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography in evaluation of hepatobiliary malignancies

P Laksmana Chandra , P Shravan Kumar, M Umadevi, M Ramanna

Department of Gastroenterology, Gandhi Hospital, Hyderabad 500 003, India

Background/Aim: Hepatobiliary malignancies leading to obstructive jaundice is an important problem in GIT. In this study, we aimed at identifying efficacy of ultrasound (US), magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) in evaluation of this situation.

Patients and Methods: Seventy-six patients of hepatobiliary malignancies presenting with obstructive jaundice who underwent US, MRCP and ERCP over a period of 3 years from 2010-20013 were included. Demographic, clinical, biochemical and ultrasonographic parameters were recorded. Other imaging modalities like MRCP were recorded. ERCP findings were analyzed and biopsy details were noted.

Results: Of the 76 patients 40 males (53 %); median age 42 years; range 35-68 years and 36 females (47 %); median age 40 range 37-55  years. The clinical presentation include jaundice 76 (100 %), abdominal pain 25 (38 %), vomiting 15 (23 %), anorexia 25 (38 %), loss of weight 20 (30 %).

  

Sensitivity

Specificity

Malignant biliary obstruction

Ultrasound

84 %

83 %

 

MRCP

94.4 %

88.8 %

 

ERCP

95 %

90 %

The spectrum of diseases diagnosed include ampullary carcinoma 36 (47%), hilar cholangiocarcinoma 24 (32%), distal cholangiocarcinoma 10 (13  %), carcinoma gallbladder 3 (4  %), metastatic liver disease 2 (3  %), hepatocellular carcinoma 1 (1  %).

Conclusion: The most common cause of hepatobiliary malignancy presenting with obstructive jaundice in this study is ampullary carcinoma followed by hilar cholangiocarcinoma. The sensitivity and specificity of ERCP and MRCP are similar in diagnosis of malignant biliary stricture.

GB-03

To evaluate the role of biliary drainage and chemotherapy in icteric nonresectable gallbladder carcinoma patients

R R Sinha , A Kumar, V M Dayal, R N Priyadarshi

Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Shiekhpura, Patna 800 014, India

Background and Aim: Gallbladder carcinoma (GBC) is the commonest biliary cancer and most common cause of obstructive jaundice in north India. Most patients present in its advanced unresectable stage and so palliative therapy and chemotherapy remains as an option in these patients. This study aims to see the survival benefit of biliary stenting and chemotherapy over biliary stenting with best supporting care (BSC) in cases of unresectable GBC patients.

Patients and Method: Forty-two patients of unresectable GBC having jaundice (bil >5 mg/dL) were included in the study between April 2012 to August 2013. Biliary drainage with SEMS was done in all patients by PTBD or ERCP. After decrease of bilirubin to <3 mg/dL patients were randomly assigned to either chemotherapy group or best supportive care group. Chemotherapy drugs used were Gemcitabine (1000 mg/m2) and Oxaliplatin (100 mg/m2). Six cycles of chemotherapy were given. Patients were assessed 3 monthly by CECT and response was evaluated according to RECIST criteria. Overall median survival was calculated in both groups. Patients were followed up to 1 year or till death.

Results: Total 42 patients, 14 men and 28 female were analyzed. Median age of patient was 50.5 years (30-65 years). Mean level of serum bilirubin in chemotherapy group and BSC group were 18.3 mg/dL (95 % CI, 15.8-20.7 mg/dL) and 19.6 mg/dL (95 % CI, 16.3-22.9 mg/dL) respectively. Overall survival in chemotherapy group was 6.6 months (range 1.5-14.6 months) as compared to 2.8 months (range 2-5.2 months) in BSC group. Survival was significantly better in chemotherapy group (p=0.0001).

Conclusion: There is significant survival benefit of chemotherapy with Gemcitabine and Oxaliplatin after biliary drainage with SEMS in nonresectable gallbladder carcinoma patients presenting with biliary obstruction as compared to biliary drainage and BSC.

GB-04

An audit of bile and brush cytology in patients with malignant obstructive jaundice undergoing ERCP at a tertiary cancer centre in India

Mukund Virpariya , Shaesta Mehta, Prachi S Patil

Department of Digestive Disease and Clinical Nutrition, Tata Memorial Hospital, Mumbai 400 012, India

Background: Patients with hepato-pancreatico-biliary (HPB) malignancies often undergo an endoscopic retrograde cholangiopancreaticography (ERCP) for obstructive jaundice (OJ). The diagnostic sensitivity of brush cytology at ERCP is reported to be 20 % to 70 %. We performed a retrospective audit from a prospectively maintained endoscopy database for biliary cytology.

Methods: We analyzed bile and brush cytology in 271 consecutive subjects with HPB malignancies and OJ referred for ERCP at the Tata Memorial Hospital over 18 months. Seven subjects with non-HPB malignancies were excluded.

Results: Two hundred and sixty-four subjects were included. The commonest site of primary tumor was gallbladder in 122 (46 %), ampulla in 62 (23.5 %), pancreas in 46 (17.4 %), and cholangiocarcinomas in 26 (9.8 %). Eight subjects had a biliary stricture under evaluation. Bile was sent for cytology in 20 subjects (range 2-8 mL), brush cytology was done in 12 and both were done in 18 subjects. Bile cytology report was adenocarcinoma in 8 subjects, atypical cells suspicious of adenocarcinoma in 12 subjects and no malignancy in 18 subjects. Brush cytology report was adenocarcinoma in 10 subjects, atypical cells suspicious of adenocarcinoma in 10 subjects and no malignancy in 10 subjects. Bile cytology was positive in 21 % and brush cytology positive in 33 % subjects with both positive in one subject. In all the rest, diagnosis of malignancy was confirmed by imaging guided FNAC or biopsy later.

Conclusions: Biliary cytology seems to be equally effective as brush cytology for obtaining a tissue diagnosis. Prior dilatation of strictures and sending more quantity of bile for analysis may further improve the yield.

GB-05

Sensitivity of brush cytology in cases of extrahepatic cholangiocarcinoma in a tertiary care hospital

D jaya Chandran , Shravan Kumar, M Uma Devi, M Ramanna

Gandhi Hospital, Musheerabad, Hyderabad 500 003, India

Aim of the Study: Tissue diagnosis is essential for the management of patients with malignant biliary obstruction, particularly in patients who have an in-operable disease, in this modern era advanced cross-sectional imaging, particularly to decide upon various palliative treatments.

Materials and Methods: We prospectively studied 31 patients, from 2012- 2014 over a period of 2 years, with extrahepatic cholangiocarcinoma suggested by clinical, biochemical and radiological features, 26 patients were included in the study and 5 patients were excluded due to inadequate data. Brush cytology (with a cytomax-2 double lumen cytology brush from Wilson Cook-U.S.A. and later non-wire guided cytology brush form NEON Medical Systems-India, and the scra**s were smeared over glass slides and fixed formalin and submitted to pathology lab) was obtained from the stricturous segment during endoscopic retrograde cholangiopancreatography.

Results: The study comprised of 26 patients (12 males, 14 females), with a mean age of 52 years (range 38-62 years). The level of obstruction was at hilum in 17 (66 %) cases and distal in 9 (34 %) cases. Brush cytology was positive for malignancy in 10 cases (38 %). Six cases out of 11 with cytomax-2 (54 %) came positive but only 4 among 15 cases (24 %) with non-wire guided brush.

Conclusion: Brush cytology form malignant biliary strictures with a standard wire guided cytology brush yields a sensitivity of 54 % avoiding CT|US guided FNAC.

GB-06

Multicenter comparative evaluation of endoscopic placement of expandable metal stents for malignant distal CBD obstruction by ERCP or EUS-guided approach

Vinay Dhir 1 , Takao Itoi 2 , Mouen A Khashab 3 , Do Hyun Park 4 , Anthony Yuen Bun, TEOH 5 , Rajeev Attam 6 , Ahmed Messallam 3 , Shyam Varadarajulu 7 , Amit Maydeo 1

1Department of Endoscopy and Endosonography, Baldota Institute of Digestive Sciences, Mumbai 400 012, India, 2Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan, 3Division of Gastroenterology and Hepatology, Johns Hopkins Hospi

Background: A single session EUS-guided biliary drainage (EUS-BD) may be a viable alternative to ERCP in patients with malignant distal CBD obstruction. There is no study comparing EUS-BD and ERCP for relief of distal malignant biliary obstruction.

Objective: To compare the outcomes of self-expandable metallic stent (SEMS) placement for malignant distal biliary obstruction by ERCP and EUS-BD.

Study Design: Multicenter retrospective analysis. Setting: Tertiary referral centers. Patients: Malignant distal CBD obstruction patients requiring SEMS placement. Interventions: Patients in EUS-BD group underwent EUS-guided choledochoduodenostomy (EUS-CDS) or antegrade (EUS-AG) procedures following one or more failed ERCP attempts. Patients in ERCP group underwent retrograde SEMS placement. Main outcome measures: Composite success (the ability to complete the intended therapeutic procedure in a single session and resulting in >50 % fall in bilirubin over 2 weeks).

Results: There were 208 patients (104 treated with ERCP and 104 treated with EUS-BD (68 EUS-CDS, 36 EUS-AG). SEMS placement was successful in 98 patients in ERCP and 97 in EUS-BD (94.23 % vs. 93.26 %, p=1.000). The frequency of adverse events in the ERCP and EUS-BD group were 8.65 %, and 8.65 %, respectively. Postprocedure pancreatitis was higher in the ERCP group (4.8% vs. 0, p=0.059). The mean procedure times in ERCP and EUS-BD group were similar (30.10 and 35.95 minutes, p=0.05). Limitations: Retrospective analysis.

Conclusions: In patients with malignant distal CBD obstruction requiring SEMS placement, short-term outcome of EUS-BD is comparable to ERCP.

GB-07

Novel ex vivo model for hands-on training and teaching in EUS-guided biliary drainage: Creation of Mumbai EUS-stereolithography/3D printing bile duct prototype (with videos)

Vinay Dhir 1 , Takao Itoi 2 , Paul Fockens 3 , Manuel Perez-Miranda 4 , Mouen Khashab 5 , Dong Wan Seo 6 , Ai Ming Yang 7 , Ho Khek Yu Lawrence 8 , Amit Maydeo 1

1Baldota Institute of Digestive Sciences, Mumbai 400 012, India, 2Tokyo Medical University, Tokyo, Japan, 3Academic Medical Centre, Amsterdam, Netherlands, 4Valladoid University Medical School, Valladoid, Spain, 5Johns Hopkins University School of Medicine,

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative rescue method in patients with failed ERCP. Opportunities for teaching and training are limited due to low case volume at most centers.

Objective: To evaluate a stereolithography/3D printing bile duct prototype for teaching and training in EUS-BD.

Design: Prospective observational feasibility study.

Setting: Tertiary referral centre.

Subjects: Twenty endosonographers attending an interventional EUS workshop.

Intervention: A prototype of a dilated biliary system was prepared by computer aided design and 3D printing. The study participants performed guidewire manipulation and EUS-BD procedures (antegrade and/or choledochoduodenostomy) on the prototype. Participants scored the device on a scale of 1-5 via a questionnaire. Participants success rate for various steps of the EUS-BD procedure was noted.

Main Outcome Measures: Subjective and objective evaluation of the prototype regarding its overall applicability, quality of X-ray and EUS images, and four steps of EUS-BD procedure; needle puncture, guidewire manipulation, tract dilation, stent placement.

Results: Fifteen participants returned the questionnaire and 10 completed all four steps of the EUS-BD. The median score for overall utility was 4, while that for EUS and ultrasound views was 5. Participants with experience of >20 EUS-BD procedures scored the prototype significantly lower for stent placement (p=0.013), and equivalent for needle puncture, tract dilation and wire manipulation. The success rate of various steps was 100 % for needle puncture and tract dilation, 82.35 % for wire manipulation, and 80 % for stent placement. The mean overall procedure time was 18 minutes

Limitations: Small number of participants.

Conclusion: The 3D printing bile duct prototype appears suitable for teaching and training in various steps of EUS-BD. Further studies are required to elucidate it’s role.

GB-08

Clinical and demographic profile of choledochal cysts at tertiary care Hospital, Mumbai

Pravir Gambhire , Ketaki Gharpure, Sunil Pawar, Ravindra Surude, Rajiv Joshi, Pravin Rathi

Department of Gastroenterology, Topiwala National Medical College and B Y L Nair Hospital, Mumbai Central, Mumbai 400 008, India

Background: A classification scheme for cysts of the extrahepatic bile ducts (choledochal cysts) was proposed initially in 1959. It was expanded in 1977 to include intrahepatic cysts and further refined in 2003 to incorporate the presence of an abnormal pancreaticobiliary junction (APBJ). Advances in imaging, together with advances in surgery have greatly influenced the diagnosis and management of choledochal cysts.

Aims: 1. To study the demographic profile of patients presenting with choledochal cyst. 2. To study the common type of choledochal cyst in the study population. 3. To study the surgical outcome of patients with surgery.

Materials and Methods: Detailed analysis of 11 patients who were diagnosed to have choledochal cysts either on MRCP or ERCP was done at B Y L Nair Hospital over a year.

Results: The mean age of the patients was 48 yrs (range 32 -92). The male to female ratio was 1:3. The most common choledochal cyst being type 1 (82 %). Six patients presented with intermittent abdominal pain. Four patients presented with dyspeptic symptoms, while 1 patient presented in cholangitis. Ten patients underwent the cyst excision. One patient denied surgery, histopathology of all the excised cyst did not reveal malignancy.

Conclusions: 1. The male to female ratio of choledochal cyst was 1:3. 2. The most common presentation was intermittent abdominal pain. 3. The most common biliary cyst was type I choledochal cyst. 4. None of operated patient had malignancy in the cyst.

GB-09

Endotherapy in extrahepatic biliary obstruction- Our centre experience

S Sukumaran , K Muthukumaran, G Ramkumar, R Balamurali, T Raj Kumar Solomon, A Murali, P Ganesh

Department of Digestive Health and Diseases, Kilpauk Medical College, Chennai 600 010, India

Introduction: Extrahepatic biliary obstruction (EHBO) leads to cholestatic jaundice due to inability of conjugated bilirubin to be secreted into the duodenum due to multifactorial causes. Common causes are benign conditions like choledocholithiasis, biliary stricture, intraoperative biliary tract injury and malignant conditions like cholangiocarcinoma, pancreatic carcinoma, periampullary carcinoma. The majority of malignant biliary obstruction is due to inoperable disease, the mainstay of palliating jaundice is stent placement at ERCP.

Aim: To study the spectrum and outcome of ERCP performed in patients with obstructive jaundice due to extrahepatic biliary obstruction in our centre.

Materials and Methods: In this retrospective study (August 2012 to July 2014), 143 ERCP procedures done in patients with obstructive jaundice with EHBO were analyzed. Patients were evaluated with MRCP/CECT abdomen. Patient under conscious sedation; SVS done and selective cannulation of CBD+/-sphincterotomy and stent placement were done under fluoroscopic guidance.

Results: In 143 patients (male-76, female-67) with EHBO, 107 patients had benign lesions like choledocholithiasis (n=61-58 %); stricture (n=26-24 %), both (n=12-11 %), post op biliary tract injury (n=8-7 %) and 36 patients had malignant lesions like periampullary carcinoma (n=16-44 %), cholangiocarcinoma (n=11-31 %), Ca.GB (n=5-14 %) and Ca. pancreatic head (n=4-11 %) cannulation of CBD and stent placement was successfully done in 96 patients (90 %) and 25 patients (70 %) in patients with benign and malignant lesions respectively. CBD stone was successfully retrieved in 55 patients (71 %) with choledocholithiasis.

Conclusion: Choledocholithiasis and periampullary carcinoma were commonest benign and malignant lesions in our centre respectively. Stone retrieval and palliative biliary drainage were successfully done in majority of the patients.

GB-10

Portal cavernoma cholangiopathy - When surgical therapy fails or is not feasible

Harneet Singh , C Ganesh Pai

Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal 576 104, India

Introduction: Symptomatic portal cavernoma cholangiopathy (PCC) is seen in only 5-30 % patients with extrahepatic portal venous obstruction (EHPVO). While surgery is mainstay of treatment, inability to perform an initial nonselective shunt to successfully decompress the cavernoma before biliary drainage, not uncommon in EHPVO, may limit usefulness of this approach.

Methods: Patients with symptomatic PCC who could not undergo a definitive surgical procedure and followed up over 2-17 years at Kasturba Hospital, Manipal beginning 1997 were analyzed. They were managed with an increasing number of biliary stents (10Fr) up to maximum of 4, which were exchanged every 3-6 months or if cholangitis developed. Stents were removed if strictures had resolved at cholangiography or if an inflated balloon could be withdrawn easily.

Results: Five patients were identified [no shuntable veins (n=3) or failed shunts (n=2)]. Endoscopic therapy included papillotomy and stenting in all, balloon dilatation of strictures in 3 and stone extraction in 4. During follow up, strictures resolved in 3, who have since been stent-free for 3 months, 3 years and 4 years. In the other 2, stents had to be left in place as the strictures had not resolved at the last attempt at stent removal. All patients were asymptomatic at last follow up with none develo** evidence of secondary biliary cirrhosis.

Conclusion: Endotherapy has excellent medium to long-term outcomes in patients with PCC who are not candidates for surgery. These data suggest that endotherapy can be considered as a first line option even in patients who qualify for surgery.

GB-11

Vitamin D deficiency among pregnant Indian women: Prevalence, predictors and its relationship to gallbladder ejection fraction

Usha Dutta, Rimpi Singla, * Neelam Aggarwal, * Sanjay Bhadada, # Rakesh Kochhar, Lakhbir K Dhaliwal, *

Departments of Gastroenterology, Obstetrics and Gynecology* and Endocrinology#, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Pregnant women are at an increased risk for gallbladder (GB) stasis, an important risk factor for gallstones (GS). In nonpregnant women, we found that vitamin-D deficiency (VDD) was associated with GB stasis, which improves on supplementation. Prevalence of VDD and its relationship to GB stasis among pregnant women is not known.

Methods: Prospective study conducted at a tertiary care centre. Consecutive healthy pregnant women (12-16 weeks gestation) were enrolled. Serum 25(OH)vitamin-D was estimated and levels <20 ng/mL was considered as VDD. Risk factors and clinical features of VDD were assessed. Gallbladder ejection fraction (GBEF) was assessed by ultrasound after a standard fatty meal and <40 % was defined as stasis. Statistical analysis was performed to assess relationship of GB stasis and vitamin-D levels and identify factors associated with VDD.

Results: Median serum vitamin-D level (n=304) was 7.9 ng/mL (IQR 5.7, 12). VDD afflicted 92 % (n=280) of them. None of the women with normal vitamin-D levels had GB stasis in contrast to 20 % (56/280) in the deficient group (p=0.015). Women with VDD, had lower GBEF compared to those with normal vitamin-D [53.7-17 % vs. 59-10 %; p=0.026]. GBEF positively correlated with vitamin-D levels (r=0.117; p=0.042). Risk factors associated with low vitamin-D levels were urban residence (p=0.001); lower sun-exposure time (p=0.005); limited skin exposure (p<0.001); higher BMI (p=0.05) and higher socioeconomic status (p=0.02). Vitamin-D levels was associated with low serum calcium (=0.457; p<0.001).

Conclusion: VDD is highly prevalent among pregnant Indian women and is associated with GB stasis and lower GBEF. Vitamin-D supplementation may have a potential role in preventing GB stasis and thus GS.

GB-12

Etiology of obstructive jaundice-An ERCP evaluation

Sudhir Gupta, Amol Samarth, Neeraj Sawalakhe, Nitin Gaikwad, Sonal Gattewar

Department of Gastroenterology, Government Medical College and Super Specialty Hospital (SSH), Nagpur 400 003, India

Introduction: Obstructive jaundice poses diagnostic and therapeutic challenges in resource-limited countries. Our aim was to evaluate the ERCP findings in obstructive jaundice.

Material and Methods: This study was carried out from July 2013 to June 2014. A total of 177 patients were included underwent ERCP as per standard protocol.

Result: M:F ratio was 1.45:1. Majority of the patients 102 (57.62 %) were in the age group of 50-70 years. Fifty-seven (32.2 %) patients had either single (63 %) or multiple (37 %) CBD calculi. Thirty (16.94 %) patients had periampullary malignancy, with pancreatic and ampullary carcinoma accounting for 40 % each. Thirty (16.94 %) patients had benign biliary stricture (proximal CBD in 40 % and distally in 60 %). Fifteen (8.47 %) had choledochal cyst. Twelve (6.77 %) had gallbladder cancer with hilar involvement. Miscellaneous causes included portal biliopathy in 6 (3.38 %), Lemmel syndrome in 3 (1.69 %), post hydatid surgery biliary leak in 3 (1.69 %), postlaparoscopic cholecystectomy biliary leak in 3 (1.69 %). Juxta papillary diverticuli were seen in 9 (5.08 %) patients.

Conclusion: This study showed choledocholithiasis as the most common cause of obstructive jaundice followed by benign biliary strictures and periampullary malignancies.

GB-13

Incidentally detected ectopic ampulla of Vater in antrum in a patient of colonic tuberculosis

Gyan Prakash Rai , Rupesh Pokharna, Mukesh Jain

Department of Gastroenterology, Sawai Man Singh Medical College, J L N Marg, Jaipur 302 004, India

The ampulla of Vater (AOV) is commonly located in the posteromedial wall of the second portion of the duodenum. At times, the AOV may be found at uncommon sites such as the third and fourth portions of the duodenum, the duodenal bulb and the stomach. We found ectopic AOV in a 23-year-old female presented with complaints of continuous upper abdominal pain of mild intensity since 1 month. History of low grade fever and weight loss (not significant) was also present. Past history of abdominal Koch's was present. Except anemia examination was normal. Routine investigation including LFT, CXR, USG abdomen was normal except Hb -9 gm % and ESR-53. CT suggested circumferrential bowel wall thickening (18 mm) in ascending and transverse colon and multiple enlarged mesenteric lymph nodes and pneumobilia. Colonoscopic biopsy from colon suggestive of colonic tuberculosis. In view of pain abdomen, UGIE revealed ulcerated area near pylorus, from which bile seems to coming out. To confirm this ectopic AOV, MRCP (revealed cholelithiasis) and ERCP done. Ectopic papilla canulated through antrum, pancreatogram and cholangiogram taken. Cholangiogram showed a hook shaped configuration of distal CBD. During side viewing endoscopy no papilla was found in duodenum. These findings were consistent with an ectopic AOV. This alteration in anatomy may increase the risk of complications during papillotomy, with a theoretically higher risk of perforation as there is no sphincter of Oddi at this location. This is the first case report from India.

GB-14

Endoscopic snare ampullectomy (ESP) in ampullary tumors -A single tertiary care centre experience

Nachiket Dubale , Amol Bapaye

Department of Digestive Diseases and Endoscopy, Deenanath Mangeshkar Hospital and Research Center, Erandawne, Pune 411 004, India

GB-15

Postcholecystectomy biliary complications and endotherapy- Our experience

Y Jaipaul , K Muthukumaran, G Ramkumar, R Balamurali, P Ganesh, T Rajkumar Solomon, A Murali

Department of Digestive Health and Diseases, Kilpauk Medical College, Chennai 600 010, India

Aim: To study the spectrum and outcome of endotherapy performed in patients with postcholecystectomy biliary complications.

Materials and Methods: An observational study was conducted at our centre between September 2012 to August 2014. Patients who underwent cholecystectomy in other hospitals and our hospital who developed biliary complications were included in the study. Patients were evaluated with MRCP/CECT (abdomen). Patients with biliary complications were taken up for therapeutic ERCP in the form of balloon trolling, biliary stenting and stent packing.

Results: Out of 30 patients (male-16, female-14) who had postcholecystectomy biliary complications the pattern observed was: bile leak 3 (10 %), postcholecystectomy choledocholithiasis 7 (23 %), CBD stricture 7 (23 %), postcholecystectomy choledocholithiasis and CBD stricture 8 (27 %), biliary sludge 3 (10 %), cholangitis 2 (7 %). Cannulation of CBD and stent placement was successfully done in 27 patients with bile leak, CBD stricture and cholangitis (90 %). CBD stone/sludge was successfully retrieved in 22 patients with postcholecystectomy choledocholithiasis (72 %) in the first sitting.

Conclusion: Postcholecystectomy choledocholithiasis and CBD stricture were the commonest biliary complications in the patients who underwent cholecystectomy. Stone retrieval and biliary drainage were successfully done in majority of the patients.

GB-16

Single center review of endoscopic retrograde cholangiopancreatography

Sundeep Goyal , Ashok K Jain, Vinod K Dixit, Sunee K Shukla, Jayan K Ghosh

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India

Background and Aims: Endoscopic retrograde cholangiopancreatography (ERCP) is increasingly being procedure of choice in patients with suspected biliary obstruction with almost all ERCP is undertaken with a view to a therapeutic intervention. The aim of this study was to describe the demographics, indications, findings, and complications of ERCP.

Methods: The study was a retrospective review of patients who underwent ERCP at Gastroenterology Unit of the University Hospital of Varanasi over a 12-year period.

Results: Nine thousand and five hundred ERCP were performed between January 2002 and January 2014. Five thousand and seven hundred (60 %) patients were male. One thousand and twenty-five (10.78 %) procedures were done for diagnostic purpose and rest for therapeutic intention. Malignant obstruction was more common than benign etiology (68.2 % vs. 31.8 %). Among malignant etiology gallbladder carcinoma was commonest 2734/6479 (42.3 %) followed by carcinoma of the head of pancreas 1613/6479 (24.9 %), periampullary carcinoma 1310/6479 (20.2 %), cholangiocarcinoma 687/6479 (10.6 %), and extrinsic compression 131/6479 (2 %). Choledocholithiasis 2053/3021 (67.95 %), common bile duct stricture 725/3021 (24 %), postcholecystectomy biliary leak 90/3021 (3 %) and choledochal cyst 61/3021 (2 %), parasites 60/3021 (2 %) and miscellaneous 32/3021 (1 %) were benign causes. Acute pancreatitis, duodenal perforation and bleeding were most frequent complications. Overall, complication rate was 5.4 %. There was a trend towards reduction in complications of ERCP over time (p<.05). Stent placement was successful in 65 % of hilar obstruction and 88 % of distal obstruction.

Conclusion: ERCP is increasingly being procedure of choice for evaluation and management of biliary obstruction.

GB-17

Comparative study of fatty meal versus Drotaverine hydrochloride versus Hyoscine-N-butylbromide for duodenal antimotility and ease of cannulation during endoscopic retrograde cholangiopancreatography

S Vadivel Kumaran , T Pugazhendhi, Mohammed Ali

Madras Medical College, Chennai 600 003, India

Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure that requires considerable amount of training to be performed safely. Successful cannulation without complications usually depends on the expertise of the endoscopist. Conventionally, cannulation is facilitated with the help of Hyoscine-N-butyl bromide or Drotaverine, smooth muscle relaxants to impair duodenal contractions and sphincter of Oddi relaxation. This study is to compare the effect of fatty meal (1.7 % fat containing milk of 200 mL) vs. Drotaverine hydrochloride vs. Hyoscine-N-butyl bromide on duodenal contraction rate, to identify the ampulla, time for cannulation, adverse events during ERCP. Sixty patients admitted for ERCP with normal appearing ampulla on endoscopy at Madras Medical College and Hospital, Chennai, fulfilling the inclusion criteria were taken up for the study. Patients were subjected randomly into the three groups. Fatty meal, 200 mL of skimmed milk (1.7 % fat) was given orally, one hour prior to the procedure, to allow for gastric emptying.

Results: The difference in duodenal motility, cannulation time and success of the procedure did not show a statistically significant “p” value. Whereas, the statistical analysis showed a significant “p” value for change in pulse rate and blood pressure variation during the procedure, which was higher with Hyoscine-N-butyl bromide group.

Conclusion: In the current study 1.7 % fat containing milk of 200 mL is not inferior to the conventionally used Hyoscine-N-butyl bromide or its alternate Drotaverine for its antimotility effect on the duodenum during ERCP. The cannulation time is no different within the groups. The identification of ampulla was easier with the fatty meal group. There is a possibility of higher increase in pulse rate and blood pressure in patients with ischemic heart disease with the use of Hyoscine-N-butyl bromide. This shows milk can replace the conventionally used drugs during ERCP.

GB-18

IgG4 related autoimmune cholangiopathy

Archana Rastogi , Chhagan Bihari, Apurba Rajbongshi, Nikhil, Asit Arora, Viniyendra Pamecha, Shiv Kumar Sarin

Departments of Pathology, HPB Surgery, and Hepatology, Institute of Liver and Biliary Sciences, D 1, Vasant Kunj, New Delhi 110 070, India

Background: Immunoglobulin G4 related cholangiopathy is a biliary manifestation of IgG4 related disease and is the most common extrapancreatic site of involvement.

Aim: Clinicopathological characterization of IgG4 cholangiopathy.

Methods: Clinical, demographic and operative details were recorded from the hospital information system. Surgical specimens and liver biopsies were reviewed.

Results: Mean age was 60 years and male to female ratio was 3:2. All these patients presented with obstructive jaundice. Clinical diagnosis was hilar cholangiocarcinoma with secondary sclerosing cholangitis. CECT and MRCP were suggestive of cholangiocarcinoma. Hepatectomy specimens showed periductal or periductal with mass-forming gross morphology. Biliary system showed periductal cuffing by dense lymphoplasmacytic inflammation along with periductal fibrosis. Significant number of plasma cells showed immunohistochemical staining with IgG4. Serum IgG and IgG4 levels were raised in all the cases. Liver tissue in all these cases show features of sclerosing cholangitis with periportal or bridging fibrosis.

Conclusion: IgG4 is increasingly being recognized as an important mimicker of Klatskin tumor. Histopathological examination is essential for the diagnosis.

Pancreas

P-01

A case of pancreatico cutaneous fistula successfully managed with endotherapy: A case report

I Bharani, Shravan Kumar, M Umadevi, M Ramanna, S Pratibha

Department of Gastroenterology, Gandhi Hospital, Secunderabad 500 025, India

Introduction: Pancreatic fistulas are mostly iatrogenic. They occur as a complication of pancreatic surgery or percutaneous catheter drainage of pseudocysts (15 %). Approximately 50 % of internal and 70 % to 90 % of external pancreatic fistulas can be expected to heal with conservative management. Endoscopic treatments for pancreatic duct leaks have replaced surgical interventions in many situations. The mainstay of endotherapy for pancreatic leaks is transpapillary pancreatic duct stenting with a stent that bridges the leak if possible. Here we present a case of pancreatico cutaneous fistula which was successfully managed with endotherapy.

Case History: A 50-year-old male patient with previous history of pancreatitis and who underwent percutaneous drainage of collections 1 yr before presented with non-healing draining ulcer on the left flank. Investigations confirmed the presence of a pancreatico cutaneous fistula. Inspite of conservative management with NJ feeds, octreotide and other supportive care the ulcer showed no signs of healing. So ERCP with MPD stenting was done after which there was complete healing of the ulcer at 1 month follow up.

Conclusion: Endotherapy with transpapillary pancreatic duct stenting is an effective way of management in the case of pancreatic fistulas.

P-02

Study of glucose tolerance, C-peptide, C-peptide–to–glucose ratio in chronic pancreatitis patients

G Swathi , P Shravan Kumar, M Umadevi, M Ramanna, Ravi

Department of Gastroenterology and Biochemistry, Gandhi Medical College Hospital, Musheerabad, Secunderabad, Hyderabad 500 003, India

Aim: To evaluate and compare insulin secretion by pancreatic beta-cells in patients with chronic pancreatitis with healthy controls by functional tests.

Materials and Methods: Thirty patients of confirmed chronic pancreatitis and 30 age, sex and weight matched healthy controls are included in the study. All are evaluated by the functional tests of insulin secretion i.e. 1). Oral glucose tolerance test - fasting, 1 hr, 2 hr samples. 2) C-peptide before and after glucose ingestion. 3) Fasting C-peptide to glucose ratio. Statistical analysis: p value calculated.

Results: When compared to controls the patients had: similar fasting serum glucose levels (83+8.78, p >0.05), higher levels after oral glucose load, (144+28.33, p< 0.05), higher levels of fasting insulin (18, +6.07, p<0.05) but did not differ after oral glucose load, (17.31+6.35, p>0.05), significant decrease in C-peptide levels in fasting (1.03+0.38, p<0.05) as well as after giving oral glucose load (2.91+0.86, p<0.05), decreased C-peptide to glucose ratio (1.26 in cases, 4.09 in controls, p<0.05).

Conclusions: Early detection of beta cell area dysfunction by measuring C-peptide and fasting C-peptide to glucose ratio which are strong predictors of beta cell area help in diagnosing prediabetes in chronic pancreatic disorders.

P-03

A rare cause of acute pancreatitis: Case report

G Swathi , P Shravan Kumar, M Umadevi, M Ramanna

Department of Gastroenterology, Gandhi Medical College Hospital, Musheerabad, Secunderabad, Hyderabad 500 003, India

A 32-year-old male, nonethanolic presented to us with history of sudden onset of severe epigastric pain and vomitings since 5 days. No history of fever, pruritis. There is no history of loss of appetite and weight. On examination patient had jaundice and epigastric tenderness. Investigations revealed Hb 13g %, TLC 17000, RBS 98 mg %, BU 12 mg %, Cr 0.5 mg %, TSB 5 mg %, D.B 2 mg %, SGOT 36, SGPT 27, ALP 358, amylase 2000 u/L, lipase 10000 u/L. Both USG and CECT abdomen revealed dilated IHBR and CBD (10 mm), cholelithiasis and acute pancreatitis. ERCP revealed bulging papilla. After needle knife sphincterotomy, cauliflower like growth is seen. Cholangiogram showed dilated IHBR and CBD. A biopsy specimen from the tumor disclosed malignant cells of adenocarcinoma of ampulla. Colonoscopy was done which is normal. Serum tumor marker survey showed CA 19-9:107U/mL (normal <27U/mL), CEA:1.09 ng/mL. Finally patient underwent Whipple resection and cholecystectomy. Ampullary tumor presenting as acute pancreatitis is rare. There are only few published case reports.

P-04

Endoscopic management of internally migrated pancreatic duct stent

Suryaprakash Bhandari, Mukta Bapat, Nitin Joshi, Vinay Dhir, Amit Maydeo

Baldota Institute of Digestive Sciences, Mumbai 400 012, India

Background: Spontaneous intestinal migration of pancreatic stents is a known phenomenon. However retrieval of an internally migrated pancreatic stent poses a therapeutic challenge.

Materials and Methods: Data of patients undergoing pancreatic stenting since January 2005 was reviewed. Eight patients were found to have internal migration of the PD stent. The level of stent migration was divided into two categories: Level 1: Retropapillary migration of the stent, the proximal end till the genu (n=4). Level II: Migrated pancreatic stent with proximal end seen beyond genu (n=4). The stents were placed due to following reasons, prophylactic PD stenting after CBD stone extraction (n=2), pancreatic endotherapy for chronic pancreatitis (n=6). 5Fr stent was placed in three patients and 7Fr stent in rest of the patients. One patient has migrated pig tail stent, the rest had straight stents.

Results: PD stent could successfully be retrieved in 7 cases. Pig tail stent placed in the one patient could not be retrieved. Stent were retrieved using stone extraction balloon in one patient, rat tooth in 2 patients, over the wire snare in two patients and under Spyglass guidance in three patients. Level I migrated stents could be retrieved using rat tooth forceps and balloon (n=4), level II migrated stents required fluoroscopy guidance/spyglass guidance for stent cannulation and retrieval. Complications encountered were pancreatitis (n=2), bleeding (n=1).

Conclusions: Endotherapy of internally migrated pancreatic stents could be complex, and associated with adverse events. Deeply migrated PD stents (Level II) may require specialized methods like spyglass pancreatoscopy for stent retrieval.

P-05

Is ESWL without ERCP suitable as a primary treatment modality for patients with chronic pancreatitis in tropical countries: Does the stone load matter?

Suryaprakash Bhandari , Mukta Bapat, Nitin Joshi, Vinay Dhir, Amit Maydeo

Baldota Institute of Digestive Sciences, Mumbai 400 012, India

Background: ESWL only without ERCP has been advocated as a primary treatment modality for patients with chronic pancreatitis. However patients suitable for such a therapy are not defined.

Aim: 1. To identify the number of patients having spontaneous ductal clearance at ERCP after ESWL. 2. Measure pain relief post ESWL.

Materials and Methods: Retrospective analysis of symptomatic patients undergoing ESWL/ERCP during January 2013-June 2103. Patients were divided into low stone load category (<2 cms, n=14), high stone load category ( 2-5 cms, n=16) and very high stone load category ( 5-10 cms, n=15). ESWL was done using Dornier Delta II compact lithotripter. ERCP, pancreatic sphincterotomy and stone extraction was done three days after ESWL. Stents were placed in the duct only if PD clearance was incomplete.

Results: Forty-five patients having uniformly dilated pancreatic duct with single/multiple calculi underwent ESWL and ERCP during study period. Patients having low stone load had maximum spontaneous ductal clearance at ERCP (11/14). Patients having high and very high stone load required basket extraction of stone irrespective of good pulverization. Pain relief after ESWL was excellent in patients with lower stone load as compared to category II and category III patients.

Complications: ESWL related gastric and duodenal hematoma (n=2), self limited pancreatitis (n=4).

Conclusions: Patients having low stone load had maximum spontaneous ductal clearance at ERCP (78 %) as compared to category II and III patients and ESWL alone can be a therapeutic option in these patients. However, further prospective studies with larger patient population are required to confirm our findings.

P-06

Does intervention for pancreatic necrosis increases the risk of gastrointestinal bleeding in patients with acute necrotizing pancreatitis?

Surinder S Rana, Rajesh Gupta * , Ravi Sharma, Vishal Sharma, Puneet Chabra , Mandeep Kang ** , Deepak K Bhasin

Departments of Gastroenterology, *Surgery and **Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Gastrointestinal bleeding (GIB) is potentially fatal complication of acute necrotizing pancreatitis (ANP). There is paucity of data on effects of these interventions on risk of GIB.

Aim: Evaluate clinical and investigational profile of patients with GIB following ANP.

Methods: Sixteen patients (14 M; mean age: 39.3±12.8 yrs) patients of ANP who had GIB were retrospectively studied.

Results: Upper gastrointestinal endoscopy revealed duodenal ulcer in 1, and severe esophagitis in 1 patient. The remaining 14 patients had ANP related GIB and endoscopy revealed fistulous opening in the duodenum and stomach in 3 and 1 patient respectively. No bleeding lesion could be identified on endoscopy in remaining 10 patients. All these 14 patients also underwent computed tomographic angiography and pseudoaneurysms were identified in 4 patients. Two were successfully treated with angioembolization whereas 2 needed surgery. One patient treated by angioembolization needed surgery for worsening sepsis and died. The patients with gastrointestinal fistula had complicated course and 3 of these 4 patients died due to multiorgan failure. Of remaining 6 patients, 1 patient needed surgery for pseudoaneurysm of transverse mesocolic artery that was successfully ligated. However, this patient died due to sepsis. Rest 5 patients were managed conservatively and there was no recurrence of GIB. Of 14 patients with ANP related GIB, a previous intervention had been done in 11 patients (percutaneous drainage in 9, endoscopic drainage in 2 and surgery in 4 patients).

Conclusions: Prior intervention seems to increase risk of GIB and gastrointestinal fistulization has poor prognosis.

P-07

Clinical outcomes and prognostic significance of early versus late computed tomography in acute pancreatitis

Vishal Sharma , Surinder S Rana, Ravi K Sharma, Rajesh Gupta * , Deepak K Bhasin

Departments of Gastroenterology and Surgery*, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Guidelines recommend that contrast enhanced computed tomography (CT) should be done after 72 hours of onset of attack of acute pancreatitis (AP). However, exact time beyond 72 hours at which CT will have best diagnostic yield for local complications is not clear and whether doing a CT early in acute pancreatitis has any adverse effect on the course of disease/outcome.

Methods: We retrospectively analyzed records of 214 consecutive patients with AP and these patients were divided into two groups: Group 1 (CT done at 4-5 days of pain) and Group 2 (CT done between day 6-14 of pain). The two groups were compared for differences in clinical outcomes and prognostic information obtained from CT like detection of pancreatic necrosis, local complications and CT severity index.

Results: Of 214 patients (143 (66.8 %) males; mean age 39.87±13.52 years), 21 patients were excluded. Group 1 (early CT) included 114 patients whilst group 2 (late CT) had 79 patients. The mean CTSI was higher in late CT group (6.65±2.27 vs. 5.52±2.7, p=0.005). The incidence of persistent organ failure in early CT group was no different from late CT group. Local complications were detected more often in the late CT group (84.8 % vs. 68.4 %, p=0.011). The need for percutaneous drainage or surgery as well as mortality did not differ amongst the two groups.

Conclusions: Performing early CT does not adversely affect outcome in AP and CT done within 5 days of onset of symptoms may diagnose lesser number of local complications.

P-08

Clinical audit of patients with acute pancreatitis

Jaya Ghosh Chatterjee , A Konar, P P Bose, M Jana, M Das

Peerless Hospital, 360, Panchasayar, Garia, Kolkata 700 094, India

Purpose: Acute pancreatitis is one of the common gastrointestinal emergencies. There are many scoring system for predicting severity. BISAP score is one of them and an easy, effective tool. In this prospective study we categorized the patients. 1. According to BISAP score at admission and determined outcome, and 2. impact of IV fluid management during first 48 hrs on complication and ultimate outcome

Method: An ongoing prospective study of patients with AP admitted at our hospital, between August 2012 and July 2014. Total number of patients were 104; of which 25 were excluded (recurrent AP=6; acute on CP n=2 and 17 patients who were admitted after 5 days of onset of pain). Total 79 patients were included. BISAP score was calculated at admission and most of the patients were allocated either to ward/ITU accordingly. Patients were divided into 2 groups- A. According to time of presentation- Early (within 48 hrs n=35; among which 18 patients presented within 24 hrs) and late (between 2-5 days.) and Gr B. Based on BISAP score. Etiology-gallstone-49/79 (62 %)/ ethanol-11/79 ( 13.9 %)/post ERCP-5/79 (6.%)/unknown-14/79 (17.72 %).

Results: Total patients-79; M -52 (65.82 %), F-27 (34.17%). Age - range-12-80 years. Most were between 2nd-6th decades. Mean age -44.31. Necrotizing-17/70 (21.51 %), nonnecrotizing-62/79 (78.48 %).

Table 1 (i ) Gr-A- early admission, IV fluid resuscitation and recovery

Admission time

Recovery and discharge

Death in hospital

Total no patients, n=79

Early

(48 hrs)

34 (97.14)

1 (2.86)

35

Late (2-5 days)

39 (88.64)

5 (11.36)

44

p value

0.125

0.125

Not signifant

p value<0.05 significant

Table 1 (ii) - Gr-A- early fluid resuscitation versus necrosis

Admission time

PCV >45

Necrosis

Total patients

By 24 hrs

6 (33.33)

2 (33.33)

18

Between 24-48 hrs

6 (35.29)

4 (66.67)

17

p value

0.903

0.221

Not sig

Table 2. (i) -Gr B- BISAP score and outcome

Bisap score

Recovery and discharge

Death in hospital

Total patients, n=79

< 2

59 (98.33)

1 (1.67)

60

>2

16 (84.21)

3 (15.79)

19

p value

0.098

0.098

Not significant

Table 2 (ii)- Gr B-BISAP and necrosis on CT scan

Bisap score

Necrosis

No necrosis

Total patients=79

< 2

9 (15)

51 (85)

60

BISAP>2

8 (42.11)

11 (57.89)

19

p value

0.027

0.027

significant

Conclusion: 1. BISAP is one of the simplest and can be calculated at admission and can predict. Outcome 2. Early appropriate fluid management within 24 hours may avert necrosis.

P-09

Clinical significance of presence and extent of extrapancreatic necrosis in acute pancreatitis

Surinder S Rana, Vishal Sharma , Ravi K Sharma, Puneet Chhabra, Rajesh Gupta * , Deepak K Bhasin

Departments of Gastroenterology, and *Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Extrapancreatic necrosis (EPN) alone represents a subgroup of pancreatitis with better outcome than patients with pancreatic parenchymal necrosis (PN). However, data on clinical significance of EPN is limited and significance of extent of EPN is not known.

Methods: Two hundred and thirteen patients (136 (63.8 %) males; mean age: 39.8 ±13.2 years) with acute pancreatitis (AP) were prospectively enrolled and followed up till recovery or death. Contrast enhanced computed tomography (CECT) of each patient was evaluated for presence of PN and EPN, pleural effusion and ascites. EPN was termed extensive if it extended to paracolic gutters or pelvis.

Results: Twenty-one (9.9 %) patients had interstitial pancreatitis, 7 (3.3 %) patients had PN alone, 48 (22.5 %) patients had EPN alone and 137 (64.3 %) patients had combined PN and EPN. Patients with EPN alone had significantly higher frequency of organ failure than patients with interstitial pancreatitis. On comparison with patients with EPN alone, patients with combined necrosis had significantly higher frequency of pleural effusion (88.2 % vs. 75 %), ascites (41 % vs. 20.8 %), and need for intervention (32.6 % vs. 14.6 %). Patients with extensive EPN (n=57) had significantly higher frequency of pleural effusion, ascites and multiorgan failure (MOF) than those with limited EPN.

Conclusion: EPN alone should be considered as a separate category of AP as it has less severe course than PN but has more severe course than interstitial pancreatitis. Patients with extensive EPN in spite of having increased frequency of ascites, pleural effusion and MOF had similar outcome as compared to patients with limited EPN.

P-10

Comparative study of radiological scoring systems evaluating extrapancreatic inflammation with clinical and conventional radiological scoring systems in predicting severity and outcomes in acute pancreatitis

Vishal Sharma , Surinder S Rana, Ravi K Sharma, Mandeep Kang * , Rajesh Gupta **, Deepak K Bhasin

Departments of Gastroenterology, *Radiodiagnosis and **Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: A number of scoring systems have been developed to predict prognosis in acute pancreatitis (AP).

Aim: To compare the extrapancreatic inflammation on CT (EPIC) score and renal rim sign with clinical scores (BISAP, SIRS) and conventional CT scores (CTSI and MCTSI) in predicting persistent organ failure (POF), intervention and mortality in AP.

Methods: The demographic, radiographic, and laboratory data from consecutive patients with AP admitted in our unit over were retrospectively evaluated. The scores were evaluated by calculating receiver operator characteristic (ROC) curves and the area under the ROC (AUROC) curve.

Results: Of the 105 patients (65 males; mean age 40.6±12.9 years) included, 8 died and 71 developed POF whereas radiological/endoscopic intervention were needed in 16 patients. The mean CTSI, MCTSI and EPIC score were 5.8±3.0, 7.1±2.6 and 4.0±1.9 respectively. The AUROC for SIRS, BISAP, CTSI, MCTSI, Renal Rim Score and EPIC score in predicting POF were 0.65 (CI: 0.53-0.78), 0.75 (CI: 0.65-0.86), 0.66 (CI: 0.54-0.78), 0.70 (CI: 0.58-0.81), 0.64 (0.52-0.76), 0.71 (CI: 0.60-0.83) respectively, for radiological/endoscopic intervention were 0.50 (CI: 0.35-0.65), 0.64 (CI: 0.49-0.78), 0.51 (CI:0.36-0.66), 0.55 (CI: 0.41-0.70), 0 .51 (0.36-0.67), 0.66 (CI: 0.52-0.81) respectively, and for mortality 0.57 (CI: 0.38-0.75), 0.90 (CI: 0.83-0.97), 0.67 (CI: 0.50-0.83), 0.68 (CI: 0.51-0.85), 0.73 (CI: 0.57-0.89) and 0.77 (CI: 0.64-0.90) respectively.

Conclusion: The prognostic performance of various clinical and radiological scoring systems in AP is comparable with BISAP having the highest accuracy for predicting POF and mortality.

P-11

Pivotal role of single nucleotide polymorphisms in TGF-î 21 TNF-î±genes in chronic pancreatitis

K Sri Manjari 1 , Pratibha Nallari 2 , P Shravan Kumar 3 , B Prabhakar 4 , M Uma Devi 3 , M Ramanna 3 , Pratibha 3 , Bharani 3 , A Jyothy 1 , A Venkateshwari 1

1Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad 500 00, India, 2Department of Genetics, Osmania University, Hyderabad 500 00, India, 3Department of Gastroenterology, Gandhi Hospital, Secunderabad 500 025, India, and 4Department of Gastroenterology, Osman

Introduction: Chronic pancreatitis (CP) is a progressive inflammatory process affecting the pancreas. Transforming growth factor- Î21 (TGF-Î21) and tumor necrosis factor-α (TNF-α) gene are the key cytokines in extracellular matrix production and degradation at different levels. Single nucleotide polymorphisms (SNP) in the promoter are known to alter the production of these cytokines.

Aim: To investigate the functional significance of TGF-Î21 (C-509T) and TNF-α (G-308A) promoter SNPs in chronic pancreatitis.

Materials and Methods: The study group was composed of 120 patients with CP and 120 normal controls. The polymorphism for TGF-Î21 (C-509T) and TNF-α (G-308A) was genotyped using ARMS-PCR method, followed by agarose gel electrophoresis.

Results: The genotype distribution was 57 % of C/C, 38 % of C/T and 5 % of T/T in control subjects, whereas in CP they were 37 % of C/C, 39 % of C/T, and 24 % of T/T genotype respectively. There is an increase in the distribution of TT [OD=0.410 (0.261-0.643), p<0.0001**] of TNF in the patient group compared to control subjects.

Conclusion: Hence the TGF-Î21 (C-509T) and TNF-α (G-308A) promoter polymorphisms may be associated with the disease.

P-12

A retrospective study of pancreatic fluid collections-A tertiary care centre experience

V Kunal , B Sukanya, K Ajit, N Joshi, Y Raghavendra, S Sandip, K Chintan, S Nikhil, R Maidur, K P Bubun

Department of Medical Gastroenterology, Nizam’s Institue of Medical Sciences, Punjagutta, Hyderabad 500 082, India

Background: Course and prognosis of pancreatitis depends on the severity and presence of fluid collections.

Aims: To study the nature of fluid collections in patients with pancreatitis and its clinical and treatment outcomes.

Methods and Results: One hundred and fifty-four patients were included from January to July 2014. There were 133 (86.4 %) males and 21 (13.6 %) females. Patients with pancreatitis were classified into acute (n=71; 46.1 %), chronic (n=48; 31.18 %) and acute on chronic (n=35; 22.72 %). Age range was 11-75 years (median: 38 yrs). The etiologies were alcohol (118; 76.62 %), biliary (10; 6.49 %), idiopathic (17; 11.03 %), hyperparathyroidism (1; 0.64 %), pancreas divisum (3; 1.94 %), tropical (3; 1.94 %), SLE (1; 0.64 %) and traumatic (1; 0.64 %). Ninety out of 154 (58.44 %) had pancreatic collections, acute peripancreatic fluid collection, APFC (n=26; 28.88 %), acute necrotic collection, ANC (n=31; 34.44 %), pseudocyst (n=28, 31.11 %) and walled off pancreatic necrosis, WOPN (n=5; 5.55 %). Sixty-four out of 154 (41.56 %) patients had no collections. Forty-two out of 90 (46.67 %) patients had a single fluid collection whereas 48/90 (53.33 %) had more than one collection. The mean hospital stay in these patients were (in days) 6.9±3.9 (no collections), 8.6±4.5 (APFC), 11.7±5.8 (ANC), 7.8±4.0 (PC) and 10 ±6.5 (WOPN). Those with necrotic collections (ANC, WOPN) had a longer hospital stay (11.5±5.8 days) than those without necrosis (8.2±4.2 days) (p<0.0001). Infected collections were found in 15/90 (16.67 %) patients (APFC-1, ANC-9, PC-4, WOPN-1). Sixty-nine out of 90 (76.67 %) were managed conservatively, 7 (7.78 %) required endoscopic cystogastrostomy (PC-3, WOPN-4). Four (4.44 %) required needle aspiration (PC-3, WOPN-1), 9 (10 %) required pigtail drainage (APFC-2, ANC-3, PC-4) and 1 (1.11 %) required PD stenting (PC-1). Eight (8.8 %) patients died.

Conclusion: The incidence of pancreatitis is more in males, alcohol being the most common etiology. Fifty-eight percent of patients have one or more pancreatic fluid collections at presentation; noninfected collections being commoner than infected. Necrotic collections (ANC and WOPN) are associated with prolonged hospitalization and greater chances of infection. Most patients can be managed conservatively. Intervention may be required for chronic, necrotic and infected collections.

P-13

Post-ERCP asymptomatic hyperamylasemia - Its significance and clinical implication

S Sandip , Ajit Kumar, N Joshi, B Sukanya, Y Raghvendra, K Chintan, S Nikhil, V Kunal, K P Bubun, R Maidur

Department of Medical Gastroenterology, Nizam’s Institue of Medical Sciences, Punjagutta, Hyderabad 500 082, India

Background: Hyperamylasemia after ERCP is common. It may remain asymptomatic, but indicates pancreatitis in a fraction of patients when associated with abdominal pain.

Aim: (1) To study the incidence of post-ERCP asymptomatic hyperamylasemia (PEAH) and its clinical implication. (2) To study risk factors associated with PEAH.

Methods: One hundred and twenty eligible patients who underwent ERCP were analyzed. Serum amylase was measured pre-ERCP and 18-24 hours post-ERCP. Factors like number of attempts at cannulation, amount of contrast injected, PD cannulation, opacification of PD, acinarisation and interventions performed were noted.

Results: Overall 33/120 (27.5 %) patients developed hyperamylasemia of which 14 (11.67 %) who developed pancreatitis were excluded. Post-ERCP asymptomatic hyperamylasemia developed in 19/106 (17.92 %). Univariate logistic regression analysis of variables showed difficult cannulation (p=0.042) and PD cannulation (p=0.038) as significant risk factors for PEAH, while female gender, age greater or equal to 50 years, sphincterotomy and PD injection were nonsignificant.

Conclusion: Our work demonstrates that pancreatitis following ERCP is common complication, but that asymptomatic hyperamylasemia is even more common. Incidence of PEAH is 17.92 % in our study which is lower as compared to incidences in other previous studies (25-70 %) where it was measured within 8 hrs post-ERCP. Thus measurement of amylase is relevant only when patient has abdominal pain. Procedure related factors like difficult cannulation and pancreatic duct cannulation are significant risk factors for PEAH.

P-14

Malnutrition can persist in patients with chronic pancreatitis even after pancreatic enzyme replacement therapy

C Madhulika * , Merlin Anne Raj * , Tahurah Muqeem * , Rupjyoti Talukdar *# , D Nageshwar Reddy *

*Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500 082, India and #Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500 082, India

Introduction: Pancreatic exocrine insufficiency (PEI) in CP is treated with pancreatic enzyme replacement therapy (PERT). Studies from the west have shown that PERT is often suboptimal in terms of patient’s response. Pancreatic enzymes require adequate amount of nutritional substrates to function optimally.

Objective: Objective of this study was to evaluate nutritional intake of patients of CP.

Methods: Consecutive patients with CP attending our Department of Nutrition between April to July 2014 were enrolled. Patients were divided into 3-groups: those on PERT for over 1 yr; irregular PERT and no PERT. Evaluated parameters were: demographics, dietary intake, subjective global assessment (SGA) and nutritional assessment (anthropometry, serum nutritional parameters, QOL [SF36], clinical evidence of malnutrition).

Results: There were 26, 35 and 48 patients in the three groups respectively with mean (SD) ages of 38.2, 36.6 and 38.9 years. Proportion of patients with pain was similar in the three groups (69.2 %, 68.6 % and 64.6 % respectively). Twelve (46.2 %), 15 (42.9 %) and 24 (50 %) patients respectively had diabetes. Mild to moderate malnutrition (SGA-B) was seen in 5 (19.2 %), 15 (42.8 %) and 14 (29.1 %) patients in the three groups respectively while severe malnutrition (SGA-C) in 13 (50 %), 10 (28.6 %) and 7 (14.6 %). Total calorie intake was low in all the three groups (1366.5 kcal, 1401.2 kcal and 1427.3 kcal respectively). Even though the protein and carbohydrate intake was normal, daily fat intake was low (34.9 gm, 33.6 gm and 41.3 gm respectively). Thirteen (50 %), 5 (14.3 %) and 8 (16.7 %) patients in the respective groups received prior nutritional counseling.

Conclusion: Despite PERT and nutritional counseling, patients with CP may remain malnourished due to low dietary intake.

P-15

Economic, psychological and nutritional burden in patients with nonalcoholic chronic calcific pancreatitis in India

Pankaj Singh , Kshaunish Das

Institute of Post Graduate Medical Education and Research, 244, A J C Bose Road, Kolkata 700 020, India

Objective: To assess the impact of chronic pancreatitis (CP) on healthcare expenses, diet and nutritional status, psychology (anxiety and depression) and employment status in a tertiary medical centre in India.

Methods: In a prospective cross-sectional study of 78 nonalcoholic adult (age >18 yrs), chronic calcific pancreatitis (CCP) were compared with 156 age and socioeconomic status matched healthy controls. Validated food frequency questionnaire, hospital anxiety and depression scale (HADS) and work productivity and activity impairment questionnaire:general health (WPAI-GH) were used. Relevant clinical data, anthropometry and health care expenses and income (by recall) in the last one month were collected. Patients with any amount of alcohol intake and with any significant comorbidity except diabetes were excluded.

Results: Baseline demography of both the groups in Table 1.

Healthcare Expenses: Total healthcare cost [THC] in last 1 month, was significantly higher in patients vs. controls [6.5±10.1 ( INR X 103 ) vs. 0.1±0.1 (INR X 103) , p< 0.0001] although there was no significant difference in mean monthly income in both the groups. In 18 % CP patients, THC were as high as >200 % of the monthly income. In almost half of these patients (49 %) this healthcare expenses were met by either selling assets, loans at interest or charitable donations.

Dietary and Nutritional Status: CP patients were mostly undernourished with significant lower measures at baseline anthropometry [mid arm circumference (MAC), skin-fold thickness (SFT)]. BMI in CP patients was significantly low [19.8±3.1 Kg /m2 vs. 23.2±3.1 Kg /m2 (p<0.0001 )] with a lower mean calorie intake [1485.0±291.8 Kcal/day vs. 2093.2±348.6 Kcal/day, p<0.0001]. Fat as a percent of total calorie was significantly high in CP.

Anxiety and Depression: CP patients had a significantly higher scores for both anxiety and depression, with 35 % patients read as ‘abnormal’ high score in anxiety scale and 28 % with ‘abnormal’ depression scale.

Work Productivity/Employment status: WPAI–GH questionnaire suggested a significant higher work-hours lost due to CP [mean, 14.8±16.0 vs. 0.1±0.8, p<0.0001] with a significantly higher health problem affected productivity score in both employed and unemployed patients.

Conclusion: This study explores the multidimensional aspect of chronic pancreatitis which adversely affects the quality of life (HRQL) in a develo** country with profound impact on employment status which in turns leads to higher economic burden. Majority of patients with chronic calcific pancreatitis were malnourished with a significantly higher prevalence of anxiety and depression than general population.

Table:1

 

CP

(n=78)

Controls

(n=156)

p value

Age (mean±SD), y

33.1±10.5

31.7±7.1

p=NS

Male, %

49

67

p<0.01

Hindu, %

72

83

p=NS

Residence, %

  

p=0.03

 Urban

30

35

 

 Semi-urban

50

33

 

 Rural

20

32

 

Married, %

71

72

p=NS

SES [Kuppuswamy], %

  

p=NS

 Lower

0

0

 

 Upper lower

59

59

 

 Lower middle

31

27

 

 Upper middle

10

14

 

 Upper

0

0

 

Occasional alcohol consumption, %

0

12

p<0.01

Current smoker, %

18

8

p=0.02

Non-smoking tobacco [Khaini], %

1

5

p=NS

P-16

Prevalence of osteodystrophy in chronic pancreatitis at tertiary care centre

Rajiv Baijal, Praveen Kumar, Soham Doshi, Sandeep Kulkarni, Naveen Totla, Deepak Amarapurkar

Department of Gastroenterology, Jagjivan Ram Hospital, Maratha Mandir Marg, Behind Maratha Mandir Cinema, Mumbai Central, Mumbai 400 008, India

Aim: To study bone mineral density (BMD), vitamin D status and bone mineral parameters in subjects with chronic pancreatitis and to determine the relationship between pancreatic dysfunction and these parameters.

Methods: All patients with chronic pancreatitis diagnosed by USG, CT or EUS were included. All confounding factors were excluded. Patients were categorized according to T score as normal: >-1.0, osteopenia:-1.0 to -2.4, osteoporosis: <-2.5.

Results: Out of 45 patients, 34 male and 11 were female. Average age of patients was 38.4 years. Major etiology was alcoholism in 36 (80 %) patients. Past history of bone fracture was noted in 11 (24 %) patients. Osteoporosis was seen in 18 (40 %) patients, osteopenia in 14 (32 %) and normal BMD in 13 (28 %). Serum calcium was low in 18 (40 %) patients and all were alcoholic. Patient with alcoholic pancreatitis were more prone for osteoporosis. Average T score in alcoholics was -2.86 and in other etiologies it was -1.92. Vitamin D deficiency was seen in 84 % of patients. Duration of pancreatitis (>3 years) (10/14) (71 %), presence of complications (12/20) (60 %), late therapy (6/8) (75 %) and presence of diabetes (13/24) (54 %) significantly increased osteoporosis. Average T score in male was -2.11 and female -2.89. No statistical correlation was found between gender and osteodystrophy.

Conclusion: The prevalence of osteoporosis is significantly high in chronic pancreatitis and requires early diagnosis and treatment. Prevalence of osteoporosis was related to alcoholism, duration and complication of disease but not to gender.

P-17

Repeat attack of acute pancreatitis follows a milder course of illness

Pradeep Kumar Sidappa , Narender Dhaka, Manish Manrai, A C Arun, Ajay Gulati, Harpal Singh, Jahangeer Basha, Vikas Gupta, Thakur Deen Yadav, Saroj Kant Sinha, Rakesh Kochhar

Departments of Gastroenterology, Radiodiagnosis and Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Aims: To evaluate the outcome of patients who present with a repeat attack of acute pancreatitis (RAP) compared to those with single attack of acute pancreatitis (SAP).

Methods: All patients of AP who presented to us between 2011 and 2013 were divided into those who presented with a single attack and those with RAP. The severity, hospital stay, necrosis, type and size of collections and their outcome were recorded and compared.

Results: Five hundred and twenty-nine patients (68.1 % males) with a mean age of 39.3±13.4 yrs were included. Four hundred and seventy-three (89.4 %) presented with SAP and 56 (10.6 %) with RAP. Alcohol was the commonest etiology of SAP (42.5 %) whereas gallstones were the commonest etiology of RAP (58.9 %). More patients in the RAP group had severe pancreatitis compared to SAP {14 (8.9 %) vs. 221 (46.7 %), p=0.007}, >90 % of patients had collections in both the groups (p=0.55) with most being acute necrotic collection {38 (67.9 %) vs. 363 (78.1 %), p=0.019}. Twenty-five (44.6 %) and 2 (3.6 %) in the RAP group required percutaneous drain placement and surgery compared to 243 (51.4 %) and 65 (13.7 %) in the SAP group (p=0.34 and 0.03). Two (3.6 %) in the RAP group died compared to 85 (18 %) in the SAP group (p=0.006).

Conclusion: RAP runs a less severe course than SAP.

Outcome

SAP

RAP

p value

BISAP (>3)

160 (22.4 %)

5 (56 %)

0.019

CTSI (mean)

7.46

6.66

0.034

CRP (mean)

4568.9

1107.6

0.003

SIRS

343 (72.5 %)

23 (56 %)

<0.001

Organ failure

272 (57.5 %)

22 (39.3 %)

0.009

Venous thrombosis

117 (24.8 %)

21 (38.2 %)

0.033

Hospital stay (mean)

24.23

17.39

0.11

BISAP bedside index for severity of acute panccreatitis, CTSI CT severity index, CRP C reactive protein, SIRS systemic inflammatory response syndrome

P-18

Significance of intraabdominal pressure in the course and outcome of acute pancreatitis

Mukesh Jaysawal, Harpal S Dhaiwal , A C Arun, Pradeep Siddappa, Ashish Bhalla, Vikas Gupta, T D Yadav, Saroj K Sinha, Rakesh Kochhar

Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Increased intraabdominal pressure (IAP) in acute pancreatitis (AP) is associated with poor outcome.

Objectives: To correlate IAP with the outcome of patients with AP and study the effect of percutaneous catheter drainage (PCD) on IAP.

Methods: In a prospective observational study on consecutive patients (>18 years of age) from February 2013 to March 2014, IAP was measured at baseline and if raised, repeatedly every 6 hourly for 24-48 hours. Normal IAP was taken as- 5 mmHg, intraabdominal hypertension (IAH) as IAP >12 mmHg, and ACS as IAP >20 mmHg along with new-onset organ failure. Serum IL-6, IL-10 and IAP were correlated with the outcome of patients. IAP was compared between patients undergoing PCD and those not subjected to PCD.

Results: Of the 50 patients, 46 % had IAH. The mean IAP on day 1 in patients with and without IAH was 15.09 and 4.59 mmHg, respectively. Presence of IAH correlated significantly with APACHE II score, SOFA score, mCTSI, organ failure, infective complications, requirement of parenteral nutrition, duration of hospital stay and ICU stay, requirement of PCD and CRP levels. Serum levels of IL-6 but not IL-10 were significantly higher in patients with IAH. There was a greater decrease in IAP in patients undergoing PCD (5.2 mmHg) than in those without PCD insertion (2.5 mmHg).

Conclusions: IAH is significantly associated with the various indicators of disease severity. Insertion of PCD helps in decreasing IAH in patients of AP with fluid collections.

P-19

Gallstone pancreatitis versus alcohol related acute pancreatitis revisited

Pradeep Kumar Siddappa , Narenda Dhaka, Manish Manrai, A C Arun, Harpal Singh, Jahangeer Basha, Vikas Gupta, Thakur Deen Yadav, Saroj Kant Sinha, Rakesh Kochhar

Departments of Gastroenterology, Radiodiagnosis and Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Aims: To compare the outcome of patients with gallstone related acute pancreatitis (GAP) with alcohol related acute pancreatitis (AAP).

Methods: All patients of AP who presented to PGIMER, Chandigarh between 2011 and 2013 were included. AP patients with etiologies other than alcohol and gallstones were excluded. The severity, hospital stay, necrosis, type and size of collections and their outcome were recorded and compared.

Results: Of 419 patients (69.9 % males) of AP, 234 (55.8 %) had AAP and 185 (44.2 %) had GAP. Patients of AAP were significantly younger (36.54 yrs vs. 43.45 yrs, p 0.05 for all. One hundred and ten (47 %) patients of AAP had severe AP compared to 90 (48.6 %) of GAP (p=0.73). Thirty-three (14.1 %) in the AAP group had repeated attacks compared to 11 (5.9 %) in the GAP group (p 5 cms and number of collections-4 were also similar between the two groups (26.9 % vs. 25 %; p=0.67 and 14.4 % vs. 14.9 %; p=0.89). One hundred and twenty-nine (55.1 %) and 41 (17.5 %) required percutaneous drain placement and surgery in the AAP group compared to 94 (50.8 %) and 17 (9.2 %) in the GAP group (p=0.37 and 0.014). Forty (17.1 %) of AAP group died compared to 37 (20 %) of GAP group (p=0.44).

Conclusion: AAP patients are younger and are more prone for repeated attacks compared to GAP. Although large size and number of collections are similar in both groups, AAP patients require surgery more often.

P-20

Effect of intravenous fluid resuscitation on inflammatory markers of acute pancreatitis and its clinical outcome

Shibojit Talukder, Jayanta Samanta , Thakur Deen Yadav, Vikas Gupta, Saroj Kant Sinha, Rakesh Kochhar

Departments of Gastroenterology and Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Fluid therapy holds the key to the initial management in acute pancreatitis (AP) but definitive evidence for the type of fluid to be administered is lacking.

Aim: To evaluate the amount of fluid required in the first 7 days for resuscitation and the effect of type of fluid used on clinical outcome and inflammatory markers in patients with AP.

Methodology: All patients of AP, presenting to a tertiary care hospital in North India between July 2012 and June 2013, within 5 days of onset of pain were enrolled. Baseline recording of clinico-biochemical profile was done. Besides the usual management, all patients were infused intravenous fluids (normal saline (NS) or Ringer’s lactate (RL)) at a rate of 20 mL/kg till a CVP of 8 cm and urine output of 0.5 mL/kg/hr were achieved. Total fluid administered, clinical outcome in terms of local or systemic complications were recorded. Serum IL-6 and IL-10 levels were measured on days 0, 3 and 7.

Results: Fifty patients were enrolled (56 % males) with 58 % having severe AP. The total volume of fluid administered in both NS and RL group was similar. RL group had early resolution of organ failure (p=0.001), less infective complications (p=0.037) and hospital stay (p=0.017) with greater lowering of IL-6 levels at day 7 (p=0.043) in severe AP.

Conclusion: Resuscitation with RL was found to be more beneficial than NS in limiting various complications and reducing proinflammatory cytokines.

P-21

Impact of the type of necrosis on site of collections and outcome in patients of acute pancreatitis

Narendra Dhaka , Pankaj Gupta, Pradeep Kumar Siddappa, Harpal Singh, Vikas Gupta, Thakur Deen Yadav, Saroj Kant Sinha, Rakesh Kochhar

Departments of Gastroenterology, Radiodiagnosis and Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Aim: To evaluate the impact of type of necrosis upon site of collections and outcome in patients of acute nercrotizing pancreatitis (ANP).

Methods: One hundred and sixty-one ANP patients with fluid collections were classified according to the type of necrosis {pancreatic (I), peripancreatic (II) or both (III)) and were correlated with different sites of collection(s) within the abdominal cavity {pancreatic (A), peripancreatic (B), both (C), peripancreatic with distant (D) and at all sites (E) and outcome.

Results: Type III was the commonest type of necrosis (n=69, 42.8 %), followed by type II (n=46, 28.57 %) and type I (n=46, 28.57 %). Type I necrosis was significantly associated with type C location of collection 32 (82.6 %), whereas type II necrosis had significant association with type D location {20(43.47)} and Type III necrosis had association with type E location {59(85.5 %)} (p<0.001). Surgery, mortality, need for percutaneous drainage and ventilator were exclusively seen in type III patients {7 (10.14 %), 14 (20.28 %), 54 (78.26 %) and 19 (27.53 %)}. Duration of hospital and ICU stay were significantly associated with type III compared to type II necrosis {34.28±24.88 vs. 13.26±7.46 days, 8.17±12.96 vs. 0.89±2.72 days, p<0.001}. Hospital and ICU stay were significantly more in type II compared to type I necrosis {18.19±10.51 and 2.43±4.32 days vs. 13.26±7.46 and 0.89±2.72 days, p=0.01 and 0.04}. Patients with necrosis involving head region (n=67) exclusively required pigtail drainage {22 (32.83 %)} and surgery {7 (10.44 %} and had mortality {14 (20.89 %} compared to those without.

Conclusion: Collections develop in a compartment more than the area of necrosis. Type III patients have the worst outcome followed by type II and then type I. Necrosis involving the head of pancreas is an ominous sign.

P-22

Impact of characteristics of fluid collections on the course and outcome of acute pancreatitis

Narendra Dhaka , Pankaj Gupta, Pradeep Kumar Siddappa, Harpal Singh, Vikas Gupta, Thakur Deen Yadav, Saroj Kant Sinha, Rakesh Kochhar

Departments of Gastroenterology, Radiodiagnosis and Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Aims: To evaluate the impact of various characteristics (number, location and size) of fluid collections on course and outcome of patients of acute pancreatitis (AP).

Methods: One hundred and ninety-five patients with AP who had acute fluid collections in and around pancreas on initial imaging were divided on the basis of collection number (single vs. multiple), size (<5 cm vs. >5 cm) and different locations {pancreatic (A), peripancreatic (B), both (C), peripancreatic with distant (D) and at all sites (E)}. Outcome variables were hospital stay, ICU stay, need for ventilator and ICU care, need for pigtail drainage, surgery and mortality.

Results: One hundred and fifty-seven (80.52 %) patients had multiple and 38 (19.48 %) had single collections. Patients with multiple collections had significantly prolonged hospital stay and the need for pigtail drainage, compared to patients with single collection {22.7±20.1 days, 63 (40.12 %) and 15.1±12.4 days, 6 (15.3 %) (p=0.02 and 0.005). Surgery and mortality were exclusively seen with multiple collections {7 (4.45 %) and 14 (8.91 %)}. Patients with collections >5 cm had significantly prolonged hospital and ICU stay {25.1±20.6 and 5.02±10 vs. 11.71±9.08 and 0.56±2.01 days, (p 5 cm and type E collections. Need for pigtail drainage, duration of hospital stay and need for ICU care were seen more commonly in patients with type D and E {14 (70 %) and 53 (85 %), 23.65±11.51 and 21.27±19.09 days, 9 (45 %) and 41 (66 %)} vs. the rest.

Conclusion: Patients with multiple, >5 cm and distant collections have worse outcome.

P-23

Role of C-reactive protein in predicting severity of acute pancreatitis

Vishnu Abishek , V Babu, Muthukumaran, Ramkumar, Balamurali, A Murali, Rajkumar Solomon, Ganesh

Department of Digestive Health and Diseases, Kilpauk Medical College, Chennai 600 010, India

Aim: To study the role of C-reactive protein in predicting severity of acute pancreatitis, and comparing its efficacy with BISAP, HAPS and SIRS score.

Methodology: Prospective, observational study done in Kilpauk Medical College, Chennai, between May 2013 and February 2014. One hundred and fourteen patients of acute pancreatitis were assessed for inclusion criteria and total of sixty-four (n=64) patients of acute pancreatitis were enrolled in the study, based on revised Atlanta classification. CRP level in serum was analyzed at 48 hours of admission. All patients underwent CECT of abdomen after 5 days of admission.

Results: 85.9 % of the study population were male, with a mean age of 37.7 years, alcohol was the etiology in 68.8 % of cases. Elevated CRP levels at a cut-off of 150 mg/L, was seen in 35.9 % of the cases. CT abdomen showed necrosis in 23 patients (35.9 %), which correlated well with elevated CRP levels (p 0.002) and elevated CRP value was associated more with necrotizing pancreatitis (p 0.004). CRP predicted severe acute pancreatitis with a sensitivity of 65.2 % and a specificity of 80.5 %. The positive predictive value of CRP in predicting SAP was 65.2 % while it had a negative predictive value of 80.5 %. CRP levels correlated with BISAP, HAPS and SIRS (p 0.001).

Conclusion: C - reactive protein (CRP) of 150 mg/L at 48 hours of admission was able to predict severe acute pancreatitis in 65.1 % and acute necrotizing pancreatitis in 52.1 %.

P-24

Effect of early nasojejunal feeding in severe acute pancreatitis

Mitali Jana, Partha Pratim Bose

Calcutta Medical Research Institute, Peerless Hospital, 360, Panchasayar, Garia, Kolkata 700 094, India

Introduction: Severe acute pancreatitis has high mortality. Sepsis is a very important cause of morbidity in the later part of the disease. Early enteral feeding has been found to be of benefit in decreasing incidence of infections in severe acute pancreatitis. We studied the difference in rates of infection, morbidity and mortality in these patients with early nasojejunal (N-J) feeding as compared with those who received standard of care.

Methods: Acute pancreatitis patients admitted in ICU who had early CRP >150 mg/dL were included in the study and randomized to either N-J or standard of care (SOC) where oral/nasogastric feeding was started later. CECT scans were done between day 8- 10 to grade the pancreatitis. Those with necrosis >50 % were considered for analysis of results.

Results: Twenty-six patients were included in the study of which 10 patients received N-J feed and 16 received SOC. CT scan excluded 3 N-J group and 5 SOC patients. Six patients in the N-G group had to be put on N-J feed for later complications like sepsis, intolerance and abdominal compartment syndrome (p=0.025). Nine out of 11 (81.8 %) developed sepsis somewhere of which 5/9 (55.6 %) recovered. Though 6/7 patients in the N-J group developed sepsis but 100% recovered (p=0.092).

Conclusion: N-J feeding early in the course of severe acute pancreatitis did not affect the incidence of sepsis and mortality though a trend towards improved outcome was observed. Larger studies are required.

P-25

Role of ammonia PET CT for assessing pancreatic necrosis in patients with acute pancreatitis

S Budakoty, A Bhalla, N Khandelwal, B R Mittal, S K Sinha , J Samanta, R Prasada, P K Siddappa, R Kochhar

Departments of Gastroenterology, Internal Medicine, Radiodiagnosis and Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Due to high perfusion per gram tissue, normal pancreas shows high ammonia uptake. We assessed utility of ammonia PET CT for diagnosis of pancreatic necrosis.

Methods: Thirty-five patients with first episode of AP (24 males, age 40.6+15.1 years) underwent contrast enhanced CT scan and PET CT scan of abdomen (after intravenous injection of 370-740 MBq of 13N ammonia). Perfusion status of pancreas was assessed both visually and semi quantitatively. PET CT severity indices were calculated in a manner similar to CECT.

Results: Etiology of was alcohol in 60 % and gallstones in 34.3 %. Organ failure included acute lung injury (ALI) in 22 and acute kidney injury (AKI) in 3 (of which two had ALI also). Two patients died. AP was mild in 7, moderate in 19 and severe in 9 patients. Contrast CT was not done in 3 due to AKI. CT severity index and modified CT severity index were 5.0+2.8 and 6.3+2.6, the corresponding figures for PET CT were 5.9+2.5 and 7.08+2.3, correlation index 0.67 (p<0.05 for body of pancreas). On ROC, SUV ratio of 0.613 gave a sensitivity of 86 % and specificity of 68 %.

Conclusion: PET CT has good accuracy for assessment of severity and diagnosis of necrosis in AP and can be an alternative of contrast enhanced CT scan in patients with AKI.

P-26

Inguino-scrotal region as unusual site of extra-pancreatic collections in infected pancreatic necrosis

Saurabh Kalia , 1 Rahul Gupta, 2 Sunil D Shenvi, 3 Hemanth Kumar, 2 Rajesh Gupta, 2 Mandeep Kang, 4 Surinder Singh Rana, 5 Deepak Kumar Bhasin, 5 Ra**der Singh 2

Department of Surgical Gastroenterology1, Narayana Multispeciality Hospital, Sector-28, Pratap Nagar, Rana Sanga Marg, Pratap Nagar Sector 11, Jaipur 302 033, India, Department of Surgical Gastroenterology3, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belgaum, India, Surgical Gastroenterology Division, Department

Background: Severe acute pancreatitis often lead to pancreatic and peripancreatic collections but rarely it can lead to collections at sites remote from pancreas like mediastinum, pleural cavity, etc. Improper history and incomplete clinical examination may miss a crucial diagnosis like acute pancreatitis particularly when it presents atypically. We encountered three cases of severe acute pancreatitis presenting with inguinoscrotal infected collections managed with scrotal drainage.

Case Description: Three male patients with their age ranging from 28-48 years presented with abdominal pain and inguinoscrotal swelling. They were initially misdiagnosed as obstructed inguinal hernia, epididymo-orchitis and hydrocele respectively. Later their diagnosis of acute pancreatitis was revealed on exploratory laparotomy in one patient and CT abdomen in remaining two patients. Contrast enhanced CT abdomen in all these cases revealed extensive peripancreatic, paracolic collections tracking along the psoas muscle downwards toward pelvis. These collections were initially managed by percutaneous drainage and saline irrigation as a part of ˜Step up approach’. Two of these patients required open necrosectomy while all the patients required incision and drainage of inguinoscrotal collections. All these patients were discharged in satisfactory condition.

Conclusion: Inguino-scrotal swelling as a first presentation of acute pancreatitis is unusual. Scrotal collections appearing during course of acute pancreatitis may contribute to continued sepsis. High index of suspicion with careful history and examination along with computed tomography of abdomen and pelvis may provide an accurate diagnosis. Local drainage may be required to control sepsis and also provide an egress route for intra abdominal collections.

P-27

Does the progress of persistent organ failure affect the outcome of severe acute pancreatitis?

Pardeep Kumar * , Vikas Gupta * , Ashish Bhalla, T D Yadav * , S K Sinha # , Rakesh Kochhar #

Departments of General Surgery*, Gastroenterology# and Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Progress of persistent organ failure (OF) during the course of the disease has not been studied previously.

Aim: To evaluate impact of worsening of organ failure on outcome in acute pancreatitis.

Methods: Fifty-seven of the 75 patients of SAP with persistent OF were evaluated for the progress of OF during the course of the disease. Patients were stratified as: early (≤7 days, n=24), intermediate (8 to 14 days, n=17) and late (>14 days, n=16) groups.

Results: Thirty-three of 38 patients with isolated respiratory failure improved – 30 % in 1st, 40 % in 2nd and 15 % in 3rd and 4th week. Nine of 13 with combined renal/respiratory failure, had improvement in respiratory failure; with majority in 4th week. Eleven of 13 with combined renal/respiratory failure had shown improvement in renal failure – 46 % in 1st, 18 % in 2nd, 9 % in 3rd and 27 % in 4th week. Mortality in worsening OF was seen in 5 with isolated respiratory failure, 2 with isolated renal failure, 4 with combined renal/respiratory failure and 3 with CVS failure. Thirteen of 14 in early presentation, 10 of 12 in intermediate and late presentation had improvement in respiratory failure. Eight patients with combined renal/respiratory failure presenting early, 50 % had improvement in renal failure within 2 weeks while respiratory failure improved in 63 % of patients in 4 weeks.

Conclusion: Progress of OF during the course of the disease is a determinant of mortality. Patients presenting early with combined failure, have improvement of renal failure ahead of respiratory failure.

P-28

Effect of enteral glutamine in the outcome of severe acute pancreatitis: A randomized controlled trial

N Saheer * , Vikas Gupta * , T D Yadav * , S K Sinha # , Bikash Medhi, R Kochhar #

Departments of General Surgery*, Gastroenterology# and Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Objective: To determine the effect of enteral glutamine in the outcome of SAP.

Methods: Sixty-two patients (35 males) with mean age 42.11±13.44 years with SAP were randomized into study group (32 patients) who received enteral glutamine for two weeks and control group (30 patients). The 2 groups were followed till discharge/death. Biochemical, hematological parameters and serum albumin, were measured on day 0, 7, 14 and 28 and CRP on day 0, 7, and 14. Clinical outcome was compared between 2 groups.

Results: Gallstone was the commonest etiology (41.90 %) followed by alcohol (30.60 %). The mean duration of onset of disease to hospital admission was 4.79±4.05 days (range 1-23 days). All demographic parameters, severity indices i.e. BISAP score (2.28±1.023 vs. 2.03±.928), APACHE II at admission (10.09±4.672 vs. 9.81±4.718) and mCTSI (7.44±2.169 vs. 7.20±2.325), and serum CRP were comparable between two group. Twenty-eight day serum albumin and APACHE II score were better in study group vs. control group (3.386±0.505 vs. 2.721±0.734, p=0.025 and 6.25±3.076 vs. 10.00±3.559, p=0.07 respectively). Incidence of organ failure, local/infectious complications, need for interventions, duration of hospital and ICU stay and mortality were similar.

Conclusions: Enteral glutamine showed improvement in serum albumin and trend towards decreasing the severity of severe acute pancreatitis during the course of illness. However it did not translate into reduction in infectious complication, organ failure, need for invasive intervention, duration of hospital and ICU stay and mortality.

P-29

Functional and morphological outcome of the patients undergoing surgical treatment of chronic pancreatitis

Anil Mani * , Vikas Gupta * , T D Yadav * , S K Sinha # , N Kalra ^ , Bikash Medhi, R Kochhar #

Departments of General Surgery*, Gastroenterology#, Radiodiagnosis^ and Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Objectives: This study was conducted to evaluate the functional and morphological outcome of patients undergoing surgery for chronic pancreatitis.

Methods: Thirty-nine patients underwent surgery (Frey n=27, others n=12). Preoperative assessment was done on admission. Exocrine function was evaluated using fecal fat globule estimation and endocrine function using HbA1c estimation. Quality of life was measured using EORTC-QLQ C30 questionnaire. Pain relief was measured on basis of need for analgesics and decrease in VAS score. Postoperatively patients were followed up at or after 3 months. MRI was done at follow up to evaluate the morphological outcome.

Results: Exocrine insufficiency was detected in 76.92 % of patients postoperatively (new onset – 41 %). Endocrine insufficiency was detected in 33.3 % (new onset – 23 %). The mean BMI increased from 19.96±3.11 to 20.98±1.94 (p-value - 0.005). The mean weight gain was 3.10±9.38 kg. The mean serum albumin level increased from 4.29±.067 to 4.6± .067 (p-value - 0.041). The pain relief was 89.74 %. Quality of life improved from 30.77±21.47 to 69.23±21.13 (p-value - <0.001). The mean MPD diameter decreased from 7.7±2.66 to 3.44±1.44 mm (p-value <0.001). There was no correlation of parenchymal thickness and duct to parenchyma ratio with exocrine insufficiency.

Conclusions: Surgical treatment offers good pain relief, substantial improvement in quality of life and remarkable nutritional status improvement in chronic pancreatitis even at the cost of some amount of exocrine and endocrine function deterioration.

P-30

Use of streptokinase for enhancement of percutaneous drainage of pancreatic necrosis

Rahul Gupta 1 , Rajesh Gupta 1 , Mandeep Kang 2 , Deepak Bhasin 3 , Madhu Khullar 4 , Ra**der Singh 1

Surgical Gastroenterology Division, Departments of General Surgery1, Radiology2, Gastroenterology3 and Experimental Medicine4, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background : Percutaneous catheter drainage [PCD] is an invaluable tool for drainage of (peri) pancreatic necrosis in patients with acute necrotizing pancreatitis. Fibrinolytic agents like streptokinase have been used locally to facilitate percutaneous drainage of empyemas, liver abscesses.

Methods All the patients of severe acute pancreatitis (SAP) managed with PCD in the Division of Surgical Gastroenterology, Department of General Surgery and Department of Gastroenterology, PGIMER, Chandigarh from April 2013 to December 2014 will be included in the trial. Currently, ten patients have been randomized to placebo and streptokinase group. Patients not responding to PCD underwent necrosectomy. The primary end-points were sepsis reversal and death. The secondary end-points were streptokinase and catheter related complications, need for surgical necrosectomy, duration of hospital stay.

Results: Among the ten patients recruited, nine were males and one female. The mean age was 34.5 years [range 24-46]. The most common etiology was alcohol [50 %]. The primary end-point [sepsis reversal] was seen in four out of five patients in placebo group and in three out of five patients assigned to streptokinase group (p=0.513). Four patients expired, one in streptokinase and three in placebo group (p=0.221). Major complications occurred in six patients, three in each group. There were no streptokinase related complications. The success rate of PCD was 60 %. Three patients required necrosectomy, one in streptokinase group and two patients in placebo group.

Conclusion: This is first study of its kind to demonstrate use of streptokinase in pancreatic necrosis and its safety.

P-31

Functional and morphological outcome of the patients undergoing pancreaticoduodenectomy

R Mahendran * , V Gupta * , T D Yadav * , S K Sinha # , A Gulati ^ , B Medhi, R Kochhar #

Departments of General Surgery*, Gastroenterology#, Radiodiagnosis^ and Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Objectives: To evaluate the functional and morphological outcome; and quality of life in patients undergoing pancreaticoduodenectomy.

Methods: Forty-five patients underwent pancreaticoduodenectomy (PD) for benign and malignant diseases were evaluated for endocrine function and exocrine function atleast 3 months of surgery. Quality of life was analyzed using EORTC QLQ - c30 questionnaire and was compared with patients operated for chronic pancreatitis. Morphological outcome was evaluated by CECT abdomen. Correlation was drawn between morphological findings and endocrine and exocrine outcome.

Results: Mean duration of follow up was 12.6±11.45 months. Seven (17.95 %) developed new onset diabetes (p=0.01). Four (66 %) of previously known diabetic patient showed uncontrolled blood sugar. Thirty-three (73.3 %) had evidence of exocrine pancreatic insufficiency (EPI) as detected by fecal fat estimation. Ten (22.2 %) of patients had steatorrhea. The mean parenchymal thickness was 18.92±4.76 mm and duct to parenchymal ratio was 0.15±0.07 mm. There was no correlation (co-efficient 0.01 and 0.015) of parenchymal thickness and duct parenchyma ratio with EPI were not. The global life index after PD was significantly (78.33±12.86 vs. 69.23±21.11; p <0.01) better than the patients with chronic pancreatitis. There was no difference in the functional and symptom score.

Conclusion: Endocrine and exocrine insufficiency occurs in 17.95 % and 73.33 % patients after PD. All patients should be routinely assessed for EPI and treated accordingly. Patients after PD had better quality of life when compared with other major surgeries.

P-32

Pancreatic ductal calculous leading to gastric fistulization

Rahul Gupta, 1 Sunil D Shenvi, 2 Surinder Singh Rana, 3 Deepak Kumar Bhasin, 3 Ra**der Singh, 1 Rajesh Gupta, 1

Surgical Gastroenterology Division, Departments of General Surgery1, and Gastroenterology3, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India, and Department of Surgical Gastroenterology2, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belgaum, India

Background: Chronic calcific pancreatitis can less commonly complicate to form internal pancreatic fistulae. Most of these patients present as pancreatic ascites or pancreaticopleural fistula. Development of spontaneous pancreaticogastric fistula due to erosion by pancreatic ductal stone has not been reported in the literature.

Case Report: We report a case of chronic calcific pancreatitis with large stone in main pancreatic duct compressing upon the posterior wall of stomach leading to spontaneous pancreaticogastric fistula.

Conclusion: Chronic pancreatitis with large pancreatic ductal stone eroding into the stomach can be successfully managed by dismantling of fistula with Frey’s procedure.

P-33

Role of percutaneous drainage in management of patients with acute pancreatitis

A C Arun , A Gulati # , V Gupta * , T D Yadav * , P K Siddappa, M Manrai, S K Sinha, R Kochhar

Departments of Gastroenterology, General Surgery* and Radiodiagnosis#, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Objectives: To compare the outcomes of percutaneous catheter drainage (PCD) vs. combination of PCD and endoscopic therapy in management of fluid collections in acute pancreatitis (AP).

Material and Methods: In a review of patients of AP who underwent PCD alone (group 1) or PCD along with endoscopic therapy (group 2) for fluid collections, outcomes including resolution of fluid collection (FC), surgery, death were evaluated. PCD was done for patients who had symptomatic fluid collections or persistent organ failure. Descriptive data was described as percentages and comparative analysis was done using SPSS v17.0.

Results: Out of the 154 patients (89 retrospective and 65 prospective) 119 were in group 1 and 35 in group 2. Patients in group 2 received endoscopic therapy apart from PCD which included pancreatic sphincterotomy alone (n=9), pancreatic stenting (n=14), nasocystic drainage with endoscopic necrosectomy (n=6), endoscopic cystogastrostomy with pancreatic stenting (n=2). FC resolved in 57 patients (47.89 %) in group 1 and 27 patients (77.14 %) in group 2 (p=0.002). Thirty-five patients (29.41 %) required surgery in group 1, while only 5 patients (14.28 %) required surgery in group 2 (p=0.07). The mortality rate was 39.49 % (n=47) in group 1 and 8.5 % (n=3) in group 2 (p=0.006).

Conclusion: Non-resolution of fluid collections, requirement of surgery and mortality were significantly low in patients undergoing endoscopic therapy along with PCD when compared to patients undergoing PCD alone.

P-34

Acute pancreatitis in North India: Is it different from west? An observational study from an tertiary care hospital

Saurabh Mishra , Premashish Kar, Suresh Kumar

Department of Medicine, Maulana Azad Medical College, Bahadur Shah Zafar Marg, Delhi Gate, Delhi 110 002, India

Acute pancreatitis is a common cause of acute abdomen which can have potentially devastating consequences. Our study aims to elucidate an update of acute pancreatitis in north Indian patients at a tertiary care Hospital in New Delhi and its difference with west.

Methods: In this observational study, a total of 56 cases of acute pancreatitis were analyzed. The diagnosis of acute pancreatitis was made in the presence of suggestive clinical features and laboratory and imaging parameters. The data regarding etiology, severity and outcome were analyzed.

Results: A total of 56 patients were admitted with diagnosis of acute pancreatitis during this period. Male to female ratio was 4.01:1 with mean age of 35.5 years overall. Increasing age was found to adversely affect outcome (p=0.04). Alcohol was identified as an etiology in 33 (58.92 %) out of 56 patients, biliary stones in 7 (12.5 %) patients. Local complications included pseudocyst and necrosis in eight patients each and abscess in five patients. Pleural effusion was the most common complication occurring in 14 (25 %) of patients. Twelve out of 56 patients could not survive the acute episode.

Conclusion: North Indian males in fourth decade of their life were at a higher risk of develo** acute pancreatitis. Alcohol is the most common etiological factor in acute pancreatitis in India whereas gallstone and biliary tract disease are the majority of cases in the west. Increasing age, impaired renal function, low systolic blood pressure, high sugar levels and fever at presentation increases adverse outcome.

P-35

Efficacy of pancreatic endotherapy in chronic pancreatitis

Amol Samarth , Sudhir Gupta, Neeraj Sawalakhe, Nitin Gaikwad, Sonal Gattewar

Department of Gastroenterology, Government Medical College and Super Specialty Hospital (SSH), Nagpur 440 003, India

Introduction: Pancreatic endotherapy has gained popularity in recent years. We aim to analyze one year data in our institute for pancreatic endotherapy.

Material and Method: It was a retrospective analytical study for duration of one year from July 2013 to June 2014. Twenty-eight patients underwent pancreatic endotherapy.

Results: M:F ratio was 1:1. 14 (50 %) patients were alcoholic and 14 (50 %) were nonalcoholic. Twelve (42.85 %) patients had pancreatic ascites. Two (7.14 %) patients had pleural effusion. Ultrasonographic findings showed ascites in 10 patients, dilated pancreatic duct in 16 and MPD calculi in 7 patients. These patients underwent ERCP and endotherapy. ERCP showed dilated PD in 20 (71.42 %) and PD calculus in 10 (35.71 %). Patients with ascites had pancreatic ductal leak. These leaks were multiple and seen at 18 (64.28 %) sites; most common site noted was genu 8 (44.44 %), tail 6 (33.33 %) and body 4 (22.22 %). Pancreas divisum was seen in 3 (21.42 %) for which spincterotomy with stent placement was performed. Pancreatic pseudocyst was seen in 2 (7.14 %). Twenty-one out of 28 were benefited from the pancreatic endotherapy and 5/28 patients (17.85 %) required repeat endotherapy. Two out of 12 (16.16 %) with ascites expired due to complications.

Conclusion: Pancreatic endotherapy is safe, effective modality of treatment in chronic pancreatitis and reduces significant morbidity and mortality.

P-36

Initial treatment of primary hyperparathyroidism induced acute pancreatitis with percutaneous alcohol injection

S K Sinha, J Samanta , A Lal # , A Bhatacharya ^ , T D Yadav * , V Gupta * , R Prasada, P K Siddappa, R Kochhar

Departments of Gastroenterology, Radiodiagnosis#, Nuclear Medicine^ and General Surgery*, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Primary hyperparathyroidism (PHPT) is a rare cause of acute pancreatitis. Management involves treatment of acute pancreatitis (AP) and definitive management of PHPT.

Aim: To study profile of patients with AP secondary to PHPT and the outcome of percutaneous ethanol ablation of parathyroid adenoma.

Methods: Six patients (3 males, median age of 49.5 years) admitted between April 2012 and July 2014 with a diagnosis of hyperparathyroidism related AP were enrolled. Intact parathormone (iPTH) levels was measured and suspected patients underwent ultrasonography (USG) of neck followed by SESTAMIBI scan. Patients were managed as per standard treatment protocol for AP. For definitive treatment, parathyroid adenoma was subjected to ethanol ablation or surgery.

Results: One patient had presented with acute on chronic pancreatitis while remaining 5 (83.3 %) had presented with AP. Four (66.7 %) had severe AP with acute lung injury and 1 (16.7 %) had moderately severe AP. All had hypercalcemia. The median iPTH level was 245 pg/mL (range 67-2433). Bilateral nephrolithiasis was noted in 2 patients. USG followed by SESTAMIBI scan revealed parathyroid adenoma; on left side in 4 and right side in 2. Five had imaging guided ethanol ablation of the adenoma, 1 patient needed a repeat session of ablation therapy. One patient underwent surgery. Post procedure normalization of calcium and iPTH levels was seen in all. On a maximum follow up of 2 years, none of the patients had recurrence of pancreatitis.

Conclusion: Percutaneous ethanol ablation of parathyroid adenoma is an effective modality in the treatment of hyperparathyroidism induced AP.

P-37

EUS guided transmural drainage of WON; comparison between a new fully covered large bore wide flare metal stent (Nagi stent) versus multiple plastic stents: A single centre retrospective study

Nachiket Dubale , Amol Bapaye, Sandeep Dawawala

Department of Digestive Diseases and Endoscopy, Deenanath Mangeshkar Hospital and Research Center, Erandawne, Pune 411 004, India

Background: WON is a frequent sequel of necrotizing pancreatitis. We present our retrospective data comparing two endoscopic methods for drainage of WON.

Methods: Outcomes of patients undergoing EUS guided transmural drainage (EUTMD) using a newly designed fully covered large bore wide flare metal stent (Nagi stent) (Gr I) were compared with patients who underwent multiple plastic stents placement (Gr II). CECT confirmed suitability for endoscopic drainage. The procedure in both groups is done by a single endoscopist by standard technique. Necrosectomy was done whenever necessary. Follow up imaging was done at 72 hrs and thereafter at 2, 4, and 6 weeks. The outcomes were compared in terms of clinical success, need for surgery, complications, hospital stay and mortality.

Results: N: 21 (Gr. I ), 61 (Gr. II). The groups were comparable in terms of demographics, etiology of pancreatitis, cyst location, size, amount of debris, need of necrosectomy and no of sessions required. Symptoms resolved in 100 % of Gr. I patients vs. 73 % in Gr. II (p=0.048). No patients in Gr I required subsequent surgery vs. 20/61 (32.7 %) in Gr. II (p=0.025).

Complications: Fifteen percent in Gr. I vs. 37 % in Gr. II (p= 0.016). Mean hospital stay was 4 days (1-33) in Gr. I vs. 8 (4-65) in Gr II (p=0.012). Mortality was none in Gr. I vs. 6.5 % (4/61) in Gr. II (p= 0.22).

Conclusions: The Nagi stent™ is effective and safe for EUTMD of WON. It offers distinct advantage over plastic stents. Prospective studies are warranted.

P-38

Effects of Allium sativum on molecular markers of fibrosis in rat model of chronic pancreatitis

Surendra Sharma , Satya Vati Rana, Ritambhra Nada * , Surinder Rana, Samir Malhotra # , Deepak Kumar Bhasin

Departments of Super Speciality Gastroenterology, Histopathology*, and Pharmacology#, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background: Allium sativum (Garlic) is considered effective antioxidant. This study aimed to investigate the effect of Allium sativum on molecular mechanism involved in fibrosis of L-Arginine induced chronic pancreatitis in rats.

Methods: Eighteen Wistar rats of either sex were divided equally into 4 groups. Group 1 (controls): rats were given IP injections of normal saline on day 1, 4, 7, 10, 13, 16 and 19 and water intragastrically daily 2 days before starting IP injections. Group 2: L-arginine hydrochloride (250 mg/100 g bw/day) IP in 2 repeated doses of 1 hr interval on day 1, repeated with 250 mg/100 g bw/day, on day 4, 7, 10, 13, 16 and 19. Group 3: rats in this group received oral administration of freshly homogenized Allium sativum (0.25 g/kg bw/day) started two days before induction of chronic pancreatitis as per group 2. Pancreatic tissues were histologically examined by H & E and Masson’s Trichrome stains. mRNA levels (densitometry analysis) of transforming growth factor-Î21 (TGF-Î21), fibronectin 1, collagen-α1(I), matrix metalloproteinase 9 and tissue inhibitor of matrix metalloproteinase 1 and 2 were performed by reverse transcription polymerase chain reaction.

Results: Allium sativum, supplementation significantly reduced inflammation and fibrosis histopathologically. Allium sativum, down-regulated significantly (p<0.05) the mRNA expression of TGF-β1, fibronectin 1, collagen-α1(I), TIMP-1, TIMP-2 and significantly up-regulated (p<0.05) expression of MMP-9 in pancreatic tissue of L-arginine induced CP.

Conclusions : Oral administration of Allium sativum, down-regulates genes responsible for fibrosis in L-arginine induced CP rats. Therefore, it can be a novel option for alleviating fibrotic process in CP.

P-39

Endoscopic management of pain in chronic calcific pancreatitis-A study from a tertiary care hospital

G Manigandan , S Sukumaran, K Muthukumaran, G Ramkumar, R Balamurali, T Rajkumar, A Murali, P Ganesh

Department of Digestive and Health Diseases, Kilpauk Medical College, Chennai 600 010, India

Background: Pain is the most distressing symptom of chronic calcific pancreatitis (CCP). Pharmacotherapy, endotherapy, and surgical options are exercised with variable success for pain management. Present study evaluated the role of endotherapy in relieving pain in CCP.

Aim: To assess the role of endotherapy to relieve pain in patients with CCP.

Patients and Methods: Study was conducted between February 2012 and February 2014. Adult patients presenting with pain suggestive of being pancreatic origin and showing radiological features of CCP on contrast enhanced CT abdomen were prospectively enrolled after obtaining written informed consent. the role of endotherapy for the relief of obstruction of the pancreatic duct (PD) and bile duct, closure of PD leaks and drainage of pseudocysts and their efficacy of pain relief was assessed.

Results : Total of 18 patients were enrolled. Twelve (66 %) males and 6 (34 %) females. 6 (34 %) had CBD stricture, 3 (16 %) had PD stricture, 4 (22 %) had MPD calculi, 3 (16 %) had pseudocyst, 2 (11 %) had only pain. Ten PD and 6 CBD cannulations were done successfully. All the patients were subjected to single sitting of endotherapy. Incidental pancreatic leak was detected in 3. Among 16 patients undergone endotherapy 11 (61 %) got significant relief from pain.

Conclusion: Endoscopic management plays a specific role as primary interventional modality to relieve pain in patients with CCP. It is also utilized as a bridge to surgery.

P-40

Spontaneous cystocolonic and duodenal fistulas in a necrotizing pancreatitis presenting as lower gastrointestinal bleed

Harish Kumar Yedla

Narayana Medical College, Chinthareddypalem, Nellore 524 002, India

Colonic fistula is a rare complication of necrotizing pancreatitis that can occur spontaneously or postsurgical procedures. Here we are reporting a case of spontaneous cystocolonic and duodenal fistulas presenting as lower GI bleed. Twenty-seven-year-old male presented with pain abdomen and vomiting and CECT abdomen suggestive of necrotizing pancreatitis and treated conservatively. After 1 month he presented with pain abdomen, repeat CECT abdomen suggestive of walled off pancreatic necrosis, and UGI endoscopy showing a fistulous opening in D1-D2 junction and treated with cystoduodenostomy. Initially he improved. One week later he presented with lower GI bleed and significant hemoglobin drop. UGI endoscopy was normal and colonoscopy suggestive of fistula near spleenic flexure. CT abdomen showing another collection in tail of pancreas and abdominal angiography was normal. He was treated with intravenous fluids and blood transfusions and other supportive measures. Presence of two spontaneous fistulas in a patient with pancreatitis is rare. Early diagnosis and appropriate treatment improves outcome.

Surgical Gastroenterology

SG-01

Intersphincteric resection and hand sewn colo-anal anastomosis for low rectal cancer – Short-term outcomes in the Indian setting

Vishwas Pai , Ashwin Desouza, Jean, Suprita Arya, Prachi Patil, Reena Engineer, A P Saklani

Tata Memorial Hospital, E Borges Marg, Parel, Mumbai 400 012, India

Introduction: The rectum remains a predominant subsite of colorectal cancer in the Indian population. Unique to the Indian setting are significant social repercussions associated with a permanent stoma. On account of this, many patients who are advised abdominal perineal excision of the rectum (APER) default treatment. Accurate demonstration of the intersphincteric plane with magnetic resonance imaging (MRI), has made intersphincteric resection (ISR) a viable option. This study is aimed at determining the feasibility and oncological adequacy of ISR in the Indian scenario.

Material and Methods: All patients with low rectal cancer who underwent an intersphincteric resection at the Tata Memorial Centre from July 2013 to July 2014 were included. Patients with invasion of the external sphincter and suboptimal preoperative sphincter function were excluded. Following standard preoperative staging, patients with a threatened circumferential resection margin (CRM) and/or mesorectal nodes were given preoperative chemoradiotherapy. The oncological adequacy of the procedure was evaluated in terms of margin positivity (distal and circumferential resection margins) and lymph node yield. Short-term perioperative outcomes included 30 day mortality, postoperative morbidity, anastomotic leaks and length of hospital stay.

Results: Forty-eight patients with low rectal cancer and a median age of 38 years underwent intersphincteric resection during the defined study period. Thirty-five patients (73 %) underwent open surgery whereas 13 patients received a laparoscopic resection. The median blood loss and hospital stay was 300 mL and 7 days respectively. Four patients had an involved CRM of which one had multifocal positivity and underwent APER. Median distal margin was 1.3 cm with involved distal margins in two patients who underwent APER. The quality of total mesorectal excision (TME) was satisfactory in all patients with a median lymph node yield of 10 nodes. Sixteen patients have undergone ileostomy reversal. Manometry at the time of reversal revealed decreased squeeze pressure in two of sixteen patients. At three months after the ileostomy reversal, five out of seven evaluable patients were fully continent.

Conclusions: Intersphincteric resection is feasible and oncologically safe in selected patients with low rectal cancer. Long-term functional and oncological outcomes are essential before it can be considered a viable alternative to APER.

SG-02

Extralevator adomino perineal resection-Short-term oncological and clinical outcomes in comparision with conventional procedure

Vishwas Pai , Ashwin Desouza, Suprita Arya, Prachi Patil, Reena Engineer, A P Saklani

Tata Memorial Hospital, E Borges Marg, Parel, Mumbai 400 012, India

Objectives: Feasibility of extralevator abdomino perineal resection [EAPER] with regard to the circumferential resection margin [CRM] and postoperative complications.

Material and Methods: Patients with low rectal cancer who underwent abdomino perineal resection in TMH during the period of one year from July 2013 to June 2014 were included. All patients underwent standard set of investigations for proper staging and those with threatened CRM were given preoperative chemoradiotherapy whereas others were offered upfront surgery. Surgery was performed 6-10 weeks after the end of chemoradiotherapy. Short-term oncological outcomes included CRM and number of nodes dissected. Clinical outcomes included postoperative wound complications, need for plastic reconstruction and hospital stay.

Results: Ninety patients with low rectal cancers underwent abdomino perineal resection during the defined study period. Out of these 27 had undergone EAPER. Among those who underwent EAPER, 12 (63 %) underwent open resection and rest underwent laparoscopic resection. Plastic reconstruction was done in 3 (15 %) with prolene mesh also used in one of the patients. Median blood loss was 500 mL and median hospital stay was 9 days. Four (21 %) developed wound complications and majority were managed conservatively. Circumferential resection margin was involved in 1 patient and median number of nodes was dissected was 9. Intraoperative rupture occurred in two patients.

Conclusions: Extralevator abdomino perineal resection is associated with significantly lower circumferential resection margin involvement and is associated with accepted perioperative morbidity.

SG-03

Analysis of 160 consecutive patients underwent upper gastrointestinal endoscopy in surgical unit B, General Hospital, Polonnaruwa, Sri Lanka

W A K Weerawardena , A S Kodikara, N P H N Darmasena, D C Dhanuksha, K G M Jeewani

General Hospital, Polonnaruwa, Sri Lanka

Introduction: We analyzed 160 consecutive patients who underwent upper gastrointestinal endoscopy (UGIE) to identify demography, presentation and endoscopy findings.

Objective: To detect a relationship with upper gastrointestinal symptoms and endoscopy finding for improved endoscopy service.

Method: Age, sex, symptoms and endoscopy findings of 160 consecutive patients who underwent UGIE at surgical unit B General Hospital, Polonnaruwa, Sri Lanka were analyzed from 16-02-2014 to 07-08-2014. Endoscopies were done with lignocaine spray into throat without sedation.

Results: There was 86 (54 %) males and 74 (46 %) females. Age range 18-87 (mean 54 years). Seventy-four (47 %) were with age between 40-59 years. Symptoms were anemia 11 (6.9 %), epigastric pain 14 (8.8 %), dysphagia 26 (16 %), hematemesis/melena 37 (23 %), suspected malignancy 6 (3.7 %), loss of appetite/weight 11 (6.9 %) abdominal fullness/discomfort/reflux 49 (30.9 %), cervical lymphadenopathy 2 (1.3 %), other 4 (2.5 %). Finding included antral gastritis 66 (41 %), normal 53 (33 %), carcinoma esophagus 4 (2.5 %), carcinoma stomach 2 (1.3 %), laryngeal carcinoma 1 (0.6 %), esophageal varices 6 (3.8 %), doudinitis 15 (9.4 %), gastric ulcer 6 (3.8 %), gastric erosions 6 (3.8 %), hemangioma 5 (3.1 %), edematous stomach mucosa 5 (3.1 %), hiatus hernia 3 (1.9 %), polyps 4 (2.5 %), candidiasis 3 (1.9 %), esophagitis 6 (3.8 %), stomach diverticula 2 (1.3 %), other 4 (2.5 %). All cancers presented with anemia/dysphagia/cervical lymphadenopathy. Gastroesophageal junction was at 39.5 cm in males and 37.1 cm in females. Normal endoscopy rate in age groups 10-29, 30-49, 50-69 years were 6/10 (60 %), 14/46 (30 %), 23/79 (29 %) in order.

Conclusion: Commonest finding was antral gastritis. Anemia, dysphagia and cervical lymphadenopathy were associated with gastrointestinal malignancy in our study. More selection criteria for indication for endoscopy in younger patients are needed to reduce the normal endoscopy rate and thereby increase the life of endoscopes.

Pediatric Gastroenterology

PG-01

Congenital ascites - Experience from a tertiary care medical centre

Sujoy Chowdhury , B R Thapa

Division of Pediatric Gastroenterology, Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

PG-02

Duodenal morphometry and small bowel permeability in children with portal hypertension

Vibhor V Borkar , Ujjal Poddar, Niraj Kumari, Suruchi Singh, Raja Roy, Surender K Yachha

Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Objective: We prospectively studied children with portal hypertension (PHT) for portal hypertensive duodenopathy (PHTD) and small bowel intestinal permeability (SIP) with the objectives of defining histopathological parameters for PHTD and to find out if any association existed among structural changes, SIP and nutritional status.

Method: SIP was assessed by using lactulose and mannitol sugar probes in 31 children with PHT (cirrhosis n=15 and extrahepatic portal venous obstruction 16) and 15 healthy children as controls. Morphometric assessment from duodenal biopsies was done in children with PHT. SIP and morphometric parameters were correlated with nutritional status and dietary intake.

Results: Among children with PHT, 48 % had PHTD defined as presence of villous atrophy (villous to crypt ratio <2.5:1), dilated capillaries (capillary diameter >16.8 μm, capillary area >151 μm2, capillary perimeter >56 μm) and thickened muscularis mucosae (>22.2 μm). Lactulose excretion alone was increased in children with PHT as compared to healthy children [median %: 0.03, 0.02 and 0.01 for cirrhosis, extrahepatic portal venous obstruction and controls respectively (p<0.01)] signifying increased paracellular permeability in PHT. Children with PHT had significantly lower z scores for height, weight and triceps skin-fold thickness (<-2SD) while no differences were found in dietary intake between patients and controls. Increased SIP, nutritional compromise and PHTD in our patients had no correlation.

Conclusion: PHT is often associated with duodenopathy. SIP does occur due to increased paracellular permeability. Compromised nutrition is attributable to intrinsic alterations caused by the disease.

PG-03

Galactosemia among Indian children: A first time report on its presentation and outcome

Moinak Sen Sarma, Anshu Srivastava, Surender Kumar Yachha, Ujjal Poddar, Amrita Mathias

Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Background: Galactosemia is a potentially fatal yet treatable disorder. There is scarcity of data regarding the natural history in Indian children.

Methods: Presentation and outcome of patients from July 2003 to June 2014 fulfilling the diagnostic criteria: 1) clinical setting for galactosemia, 2) reduced erythrocyte galactose-1-phosphate uridyltransferase enzyme activity and 3) unequivocal response to lactose-free diet (LFD) were analyzed.

Results: Twenty-four galactosemia children, constituting 2 % of neonatal cholestasis (NC) referrals were evaluated. Median age of symptom onset and diagnosis was 10 (range: 3-75) days and 55 (range:15-455) days respectively. In 22 infants with NC, majority were decompensated (71 % uncorrectable coagulopathy and 54 % ascites). Two presented as cirrhosis and portal hypertension. Associated features were hypoglycemia (63 %), cataract (54 %), seizures (29 %), sibling deaths (38 %) and transient hemolysis (16 %). Fifty percent had systemic infections, higher with disease onset 18 months age) had language delay. Hypoglycemia, seizures, age of disease onset or PELD scores were not risk factors for developmental delay.

Conclusion: Despite delay in referral, high PELD scores, cirrhosis and systemic infections, long-term liver outcome in galactosemia is rewarding though a subset have developmental delay.

PG-04

Predictors of 3-month mortality in children with decompensated chronic liver disease

Rishi Bolia , Anshu Srivastava, Surender Kumar Yachha, Ujjal Poddar

Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Introduction and Aim: Patient’s with decompensated chronic liver disease (CLD) are at an increased risk of mortality. Infections and organ failure are significant contributor’s to mortality in adult’s. However, their effect on outcome in children is not known. We aimed to study the predictors of mortality in children with decompensated CLD.

Methods: A prospective observational study was done in the Department of Pediatric Gastroenterology, SGPGIMS from March 2013 to May 2014. Seventy-five consecutive children with chronic liver disease with decompensation were enrolled. Clinical details and laboratory parameters during the hospital stay were recorded.

Results: Seventy-five children (51 boys), median age 108 (3-216) months were enrolled. Thirty-one (41.3 %) died during admission or in 3 months follow up period. These patients had a higher Child score (11.3±0.32 vs. 8.8±0.33 p=0.00). Presence of any organ failure: HE grade ¾ (58 % vs. 8/44 18.1 % p=0.001), renal failure (16.1 % vs. 0 % p=0.012), Need for ventilation (29 % vs. 0 % p=0.00) and shock (16.1 % vs. 2.2 % p=0.04) was associated with mortality. Infections were an independent predictor of mortality, increasing the mortality by two-fold (25/48 (52 %) vs. 6/27 (22 %) p=0.043). Site of infection (Bacteraemia vs. UTI vs. ascitic fluid infection or pneumonia) did not affect the outcome. Subject’s who had an adverse outcome had multiple site infections (>1 site) more often (9/31 (29 %) vs. 3/44 (6.8 %).

Conclusion: Presence of organ failure and/or infections are predictors of mortality in children with decompensated cirrhosis. They should be included in prognostic indices to improve their predictability.

PG-05

Neonatal cholestasis: Histopathological profile

Sujoy Chowdhury , B R Thapa

Division of Pediatric Gastroenterology, Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

PG-06

Choledochal cyst in neonates - Experience from a tertiary medical centre

Sujoy Chowdhury, B R Thapa

Division of Pediatric Gastroenterology, Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

PG-07

Peptic ulcer disease in children: Etiology, clinical presentation and outcome

Upender Sava , Ujjal Poddar, Surender Kumar Yachha, Anshu Srivastava, Richa Lal *

Departments of Pediatric Gastroenterology and *Pediatric Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Introduction: Peptic ulcer disease (PUD) [duodenal ulcer (DU), gastric ulcer (GU) and gastric erosions (GE)] are common in adults but not been reported in children from India. We analyzed our experience of PUD over the last 10 year.

Methods: From 2006 to June 2014, all children presented with upper gastrointestinal bleeding and diagnosed to have PUD on endoscopy were included. Details of clinical presentation, endoscopic findings and outcome were recorded in a proforma. Helicobacter pylori were diagnosed on the basis of positive rapid urease test and histology.

Results: During the study period, 306 children presented with UGI bleed (variceal 278 [EHO 269], PUD 20 [DU 8, GU/GE 12], others 8). The median age was 5.25 (range, 3 mo to 16) years with male to female ratio of 15:5. Clinical presentations were hematemesis/melena 9, melena 6, hematemesis 4, nonbleeding manifestation 1. All DU cases presented with massive UGI bleeding, 3 required surgery for failed endotherapy and 1 died. H. pylori was negative in all but one DU cases but was positive in 3 of 7 (43 %) GU/GE cases. Comparison of DU from non-DU cases revealed, younger age (<5 y: 6/8 vs. 3/12), only melena/hematochezia as presentation (6/8 vs. 0/12), need of blood transfusion (7/8 vs. 4/12), need for surgery (3/8 vs. 0/12) were significantly more (p<0.05) in DU.

Conclusions: PUD especially DU though less common may present with massive UGI bleed in children. NSAID rather than H. pylori is responsible in most DU cases. Clinical behavior of DU is more aggressive in children than GU/GE.

PG-08

β-blocker ameliorates thrombocytopenia due to hypersplenism and makes liver biopsy possible in children with liver disease

Ujjal Poddar, Upender Shava , Surender Kumar Yachha, Jaya Agarwal, Sheo Kumar * , Sanjay S Baijal * , Anshu Srivastava

Departments of Pediatric Gastroenterology and *Radiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

Background/Purpose: Thrombocytopenia due to hypersplenism precludes percutaneous liver biopsy in many cases of chronic liver disease (CLD). The aim of this study was to assess the efficacy of propranolol in correcting platelet counts (>100,000/mm3) to ensure percutaneous liver biopsy in children with CLD.

Methods: Over 8 years, 51 consecutive children (mean age 11.5±3.0 years, 34 boys) with CLD who needed liver biopsy but could not be done due to hypersplenism (platelets <100,000/mm3 and/or total leukocyte counts <4,000/mm3 with splenomegaly) related thrombocytopenia were recruited and given a 4-week trial of long-acting propranolol (1.5 to 2 mg/kg/day). Hemodynamic parameters and splenic artery hemodynamics by Doppler ultrasound were recorded before and after propranolol trial.

Results: Thirty-two (62.7 %) children responded to propranolol therapy and their mean platelet counts increased from 57.5±13.0x103/mm3 to 140.7±43.3x103/mm3, p=0.0001. Liver biopsy could be done in 29. While comparing responders with nonresponders, spleen size (7.4±3.3 vs. 12.7±4.5 cm, p=0.0001) and baseline platelet counts (57.5±13.0x103 vs. 39.5±14.5x103, p=0.0001) were found to be significant. ROC curve suggested a cut-off value of <8.5 cm of spleen and >53,000 platelets as predictors of response. With propranolol, mean arterial pressure, spleen size reduced (p<0.05) and splenic artery resistance increased significantly (p=0.005) in responders.

Conclusions: Propranolol corrects thrombocytopenia and makes liver biopsy possible in two-third of cases by reducing splenic sequestration through splenic artery vasoconstriction. The baseline spleen size and platelet counts determine the effectiveness of therapy. A trial of β-blocker is worth in cases where liver biopsy is contraindicated due to hypersplenism related thrombocytopenia.

PG-09

Bowel habits of healthy Indian children less than 2 years of age

Shrish Bhatnagar , Geetika Srivastava, Ayub Ansari

Department of Pediatrics, Eras Lucknow Medical College and Hospital, Sarfarazganj, Hardoi Road, Lucknow 226 003, India

Introduction: Bowel habits of children less than two years are quite varied and there is no definite data on stooling pattern of Indian children less than 2 years old.

Aim: Aim of our cross sectional study was to define the bowel habits of healthy Indian children less than 24 months and also study its correlation with type of feeds.

Method: Five hundred and ninety-six children aged up to 24 months were recruited from the well baby clinic of Department of Pediatrics at ERAS’ Lucknow Medical College and Hospital. Children were recruited in the following predefined age groups of: 0-14 days, 15-28 days, 1-3 months, 4-6 months, 7 -12 months and 13-24 months.The types of feeds were a) Exclusive breast feed b) Mixed Milk Feeds: Breast feed and top milk feed c) Solid: Children who were started on complementary feed. Consistency of stools were divided into solid, pasty/soft like peanut paste, runny like cream and liquid like water.

Results: The mean stool frequency in different age groups was as follows.

figure s

Correlation with feed type

Children who were on exclusive breast feed had highest frequency and variation of stools per day. Children on milk feeds (breast or mixed) in majority had pasty or runny stools while those taking complementary food had predominantly solid stools.

Conclusion: This is the first study which gives insight into combined effect of age and feed type on stooling pattern and can serve as a guide to understand the normal bowel habits of Indian children in general.

PG-10

Cow’s milk protein allergy as a cause of diarrhea in infants-A single center experience from Western India

Vishnu Biradar , Sonia Naik, Nachiket Dabale, Amol Bapaye, Vijayashri Bhide, Shital Biradar

Deenanath Mangeshkar Hospital, Erandwana, Pune 411 004, India

Aim: Cow’s milk protein allergy (CMPA) is a leading cause of food allergy in infants and children up to 5 years of age. We aimed this study to know the clinical profile of CMPA in western India and need of special formula for management.

Methods: Design: Retrospective Duration: January 2011 to May 2014. Diagnosis of CMPA was based on 1. Clinical history 2. Endoscopic mucosal biopsy showing eosinophils >6/HPF and 3. Response to milk free diet.

Results: N=26, M:F-14:12. Median age: 16.88 months (SD+/-10.27). Mean duration between presentation and introduction of cow milk: 8.18 months (0.5 - 29). Presentation: 15 (57.6 %) - chronic diarrhea and blood in stool, 10 (38.4%) - chronic diarrhea and failure to thrive. Endoscopic rectal mucosal biopsies were performed in 20 (76.9 %). Six (23 %) underwent endoscopic duodenal biopsies. Mean follow up: 7.23 months (SD +/- 5.49). Peptide based chicken formula prescribed in 9 (34.6 %) and hydrolyzed amino acid formula given to 3 (11.5 %). Remaining 14 (53 %) were managed on home made diet. Rechallenge was undertaken in 7 after parental consent. Rechallenge was done at 2 years of age or one year after stop** milk. Only one patient presented with recurrence following rechallenge.

Conclusion: CMPA is a one of the common causes of chronic diarrhea in children <5 years in western India. Rectal biopsies help in establishing diagnosis. In subset of patients (46 %), special formula based dietary modifications help in combating symptoms.

PG-11

Randomized double blinded comparison between propofol-ketamine and propofol-fentanyl combinations for sedation during pediatric esophagogastroduodenoscopy

Barath Jagadisan 1 , Rumesh Chandar 1 , A Vasudevan 2

1Departments of Pediatrics, and 2Anesthesiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Gorimedu, Puducherry 605 006, India

Background: There is a need to compare propofol requirement between propofol-ketamine and propofol-fentanyl given as non-anesthetist administered propofol sedation (NAAPS) during pediatric esophagogastroduodenoscopy (EGD).

Methods: The study was a randomized double blinded comparison of the need for additional doses of propofol in the first minute after sedation induction between propofol-ketamine (PK) and propofol-fentanyl (PF), administered by rotating trainees in pediatrics for sedation during pediatric esophagogastroduodenoscopy (EGD). Ninety-five children with American Society of Anesthesiologists class I-III between three to twelve years undergoing EGD were included and randomized to either of the groups. After midazolam premedication, children received either 0.5 mg/kg ketamine (PK) or 1 μg/kg of fentanyl (PF) followed by a mandatory 1 mg/kg of propofol. Additional doses of propofol of 0.5 mg/kg each were given to achieve sedation induction (modified Ramsay’s score level 6) and further doses were administered during the procedure as required. Ninety-two children (PK, n=47; PF, n=45) were analyzed. p<0.05 was considered significant.

Results: There was no difference in the propofol dose required for successful scope introduction and also in the need for additional propofol doses and the total additional propofol doses required in the first minute after sedation induction. Propofol injection pain (PIP) was higher in PF group (OR 1.78). The adverse events and recovery time were similar. There was no escalation of care, airway intubations, death or disability.

Conclusions: NAAP is feasible in teaching hospitals. Propofol requirement is similar in both PK and PF combination regimens but the lower frequency of PIP may favor use of PK.

Nutrition

N-01

Nutritional assessment in cirrhosis of liver

Rajiv Baijal, Praveen Kumar, Sandeep Kulkarni , Nimish Shah, Soham Doshi, Naveen Totla, Deepak Amarapurkar

Department of Gastroenterology, Jagjivan Ram Hospital, Maratha Mandir Marg, Behind Maratha Mandir Cinema, Mumbai Central, Mumbai 400 008, India

Aims and Objectives: To determine the prevalence of malnutrition in patients with cirrhosis using standard nutritional assessment tools and to compare nutritional differences between various etiologies of cirrhosis and different nutritional assessment techniques.

Methods: All adult patients with cirrhosis of liver with different etiologies were selected. Nutritional assessment was based on the following: anthropometry [mid-arm muscle circumference (MAMC)], visceral proteins, handgrip strength (HG) and subjective global assessment (SGA).

Results: Out of 150 patients with cirrhosis, 113 patients (75.3 %) were male and 37 (24.7 %) were female. The mean caloric intake was low at 16.32±2.20 kcal/kg/day. The most common etiology of cirrhosis was alcohol, seen in 69 (46 %) patients. 15.3 %, 42.66 % and 42 % patients were classified into SGA A, B and C respectively. 38 % , 84.7 %, 82 % and 74.33 % patients had malnutrition by MAMC, SGA, HG and serum albumin criteria (<3.5 mg/dL) respectively. Prevalence of malnutrition by SGA, albumin and HG was significantly higher than with MAMC (p<0.05). There was no difference in malnutrition when SGA, HG or serum albumin was compared with each other. Malnutrition was not different between alcoholics and nonalcoholic cirrhotics. Child C cirrhosis had statistically significant malnutrition as compared to Child A and Child B cirrhosis by SGA, HG and MAMC as a method of nutritional assessment.

Conclusions: Patients with cirrhosis of liver have significant malnutrition. SGA, albumin and HG are better techniques of nutritional assessment than anthropometry. The degree of malnutrition was not affected by etiology of cirrhosis.

N-02

Effect of dietary counseling on nutritional and biochemical parameters in chronic liver disease

Neha Singh , J K Choudhary, Manish Kumar Tripathi, A K Jain, S K Shukla, V K Dixit

Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India

Background: Patients with advanced liver disease should be recommended a diet providing adequate calories, proteins, minerals and vitamins. Dietary supplementation is much essential in chronic liver disease (CLD) patients, which can decrease malnutrition and infections. Oral nutritional supplements are recommended as it improves nutritional status and liver function.

Aim: To investigate the effect on nutritional and biochemical parameters in CLD who follow dietary recommendation.

Method and Materials: A total of 478 patients (M/F-401/77) with mean age were 39.9±11.8 years. The disease was diagnosed on the basis of biochemical profile, clinical features and radiological imaging. Nutritional assessment was done by using subjective global assessment (SGA) and 24 hour dietary recall method.

Results: A total of 349 cases (counseled patients) and 84 controls (non-counseled patients) group of CLD patients at baseline and after 12 month 303 in case and 71 in control group.

Table 1 Nutritional and biochemical parameters of CLD patients at baseline and after 12 months follow up of case and control group

Parameters

Baseline

case group

Baseline

control

group

p value

Follow  up

(12 months)

case group

Follow up

(12 months)

control group

p value

S protein (g/dL)

Calorie (Kcal/day)

Protein (gm/day)

HB (g/dL)

CTP score

MELD score

SGA

6.6±1.2

1301±337

43.7±11.5

10.0±2.2

9.0±1.9

17.6±5.9

14.7±3.9

6.5±1.5

1249±292

41.7±10.4

9.7±2.1

9.5±1.9

20.1±7.3

14.8±3.3

0.692

0.137

0.110

0.189

0.043

0.001

0.652

7.0±0.84

1792±320

51.2±9.6

11.7±1.8

7.5±1.4

14.7±6.5

12.5±2.9

7.0±0.84

1190±237

39.5±8.6

9.9±1.6

7.5±1.4

9.7±1.7

15.8±2.8

0.000

0.000

0.000

0.000

0.000

0.000

0.000

Conclusion: Patients of CLD who followed dietary recommendation were showing significant improvement in nutritional as well as biochemical parameters.

N-03

Percutaneous endoscopic gastrostomy in neurologically challenged patients

John , Kani Sheikh, Rathnakar Kini, Prem Kumar, Pugazhendhi, Mohammed Ali

Department of Medical Gastroenterology, Madras Medical College, Chennai 600 003, India

Background: Percutaneous endoscopic gastrostomy (PEG) is an excellent method for long-term management of enteral nutrition.

Aim of the Study: To determine efficacy, procedure related mortality, major and minor complications in neurologically challenged patients undergoing PEG.

Methods: This is a retrospective review of 28 patients who underwent PEG in our department during May 2011 to July 2014. PEG tube was placed using pull technique.

Results: PEG was successfully placed in all 28 patients, of which 24 males (85.71 %) and 4 females (14.29 %) and mean age was 42 years. The indications were neurological disorders (RTA with head injury, posterior circulation stroke, bulbar palsy) with dysphagia >4 weeks. No procedure related mortality was noted. Three patients (10.7 %) had major complications; Buried-Bumper syndrome n:1, subacute intestinal obstruction (SAIO) n:1, severe wound infection n:1. Superficial wound infection seen in 5 (17.9 %) patients. Buried-Bumper syndrome was managed by iv antibiotics and TPN and the PEG tube was removed externally. SAIO was managed by decompression by opening tube externally and resumed the feeding once bowel sounds returned. PEG tube was successfully removed in 6 patients after improvement of neurological status.

Conclusion: PEG is a safe, and effective method of long-term enteral feeding in patients with neurologic diseases. Comparing to nasoenteral feeding it has less incidence of complications like reflux induced peptic stricture and nasal injury. PEG tube can be removed once neurological deficit improves.

N-04

Assessment of nutritional status in cirrhosis and to study its impact on complications

R Vishnu Abishek , Muthukumaran, Ramkumar, Balamurali, A Murali, Rajkumar Solomon, P Ganesh

Department of Digestive Health and Disease, Kilpauk Medical College, Chennai 600 010, India

Aim: To asses the nutritional status in cirrhosis patients by anthropometry, muscle strength assessment and subjective global assessment and to compare the severity of malnourishment with the severity of liver disease.

Methodology: Interim analysis of a prospective case control study, done at Department of Digestive Health and Diseases, Kilpauk Medical College. All cirrhosis patients its more than 18 years of age, who are NOT in encephalopathy stage 2 or more are included. Normal subjects are taken as control. After assessing the CTP score and complications, nourishment status is assessed by subjective global assessment questionnaire (SGA). Anthropometric data is collected- height, weight, BMI, mid-arm circumference, triceps skin fold thickness (TSFT) using calipers (mm), mid-arm muscle circumference (MAMC) using the formula MAMC=MAC - (0.314 x TSFT), hand grip strength using dynamometer (Kg/F). SGA score B is mildly malnourished and C is severely malnourished.

Results: Forty patients are in study group, 17 in CTP C, 14 in CTP B. Thirty-three patients are malnourished according to SGA. MAMC, TSFT and handgrip strength were 21.52, 9.42, and 22.1 respectively in CTP B; 20.42, 6.23 and 20.23 in CTP C respectively, which compared to control group values of 31.2, 12.75 and 54.5 respectively, was statistically significant (p=0.001). These values were low in patients who devoted SBP. (Avg. handgrip 17.8, MAMC 19.93, TSFT 7).

Conclusion: Handgrip strength, MAMC and TSFT correlated well with CTP score and subjective global assessment in predicting malnourishment in cirrhosis patients compared to control group, and proclaims a risk for spontaneous bacterial peritonitis.

Miscellaneous

M-01

Overlap between functional dyspepsia and irritable bowel syndrome in a tertiary care hospital

P Laksmana Chandra , P Shravan Kumar, M Umadevi, M Ramanna

Department of Gastroenterology, Gandhi Hospital, Hyderabad 500 025, India

Background: Overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS) shown in various epidemiological studies. Our aim is to investigate the prevalence and risk factors for the overlap of FD and IBS based on Rome III criteria.

Methods: Patients at the gastroenterology outpatient clinic were analyzed with questionnaire. FD and IBS were defined by Rome III criteria.

Results: Questionnaires were completed by 1,520 patients (68 % female). Two hundred and fifty-eight (17 %) and 167 (11 %) of the patients were classified as FD alone and IBS alone, respectively based on Rome III criteria. FD-IBS overlap was observed in 91 (6.0 %) of the patients. Patients with postprandial distress syndrome type of FD 64 (70 %) significantly associated IBS-FD overlap than those with epigastric pain syndrome type of FD 27 (30 %). Subtypes of IBS did not differ as risk factor for FD-IBS overlap.

Conclusion: Clinical overlap of FD and IBS according to Rome III criteria is very common. This study provides need for future studies to find common pathophysiological mechanism of FD and IBS.

M-02

A propective randomized controlled study of adequacy and diagnostic yield of endoscopic ultrasound guided fine needle aspiration with and without a stylet in Indian patients

Sandeep Nijhawan , Bir Singh, Dilip Ramrakhiani, Manju Yadav, Amit Mathur, Gaurav Gupta

Sawai Man Singh Medical College, J L N Marg, Jaipur 302 004, India

Background: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is done by using EUS-FNA needle with an internal stylet by most of the endosonographers. There is no data to suggest that it improves quality of cytology specimen and it is tedious and time-consuming.

Aim: To compare EUS-FNA specimens obtained with stylet and without stylet for adequacy of specimen, amount of blood on slide, number of passes and diagnostic yield.

Methods: Patients undergoing EUS-FNA of solid lesions by one experienced endosonographer at an Indian tertiary centre from October 2013 to July 2014 were included. One hundred and fifteen consecutive patients with 128 lesions were randomized to undergo EUS-FNA with or without stylet. Cytology slides were evaluated by a single pathologist blinded to FNA technique.

Results: EUS-FNA was done with stylet in 66 lesions (group 1) and without stylet in sixty-two lesions (group 2). Site of lesion was lymph node in 67 (52.3 %), pancreas in 43 (33.6 %), liver in 8 (6.2 %), gastrointestinal subepithelial lesion in 4 (3.1 %) and others in 6 (4.9 %). The average size of lesion was 23.7±14.8. When outcomes of two groups were compared, there was no statistically significant difference in adequacy of smears (p=1.00), amount of blood on slides (p=0.92), number of passes (p=0.49) and diagnostic yield (p=0.86).

Conclusions: There was no significant difference in adequacy of specimen, amount of blood on slide, number of passes and diagnostic yield between with and without a stylet groups. The use of a stylet does not confer any advantage during EUS-FNA.

M-03

Antibiogram profile of Clostridium difficile isolates from clinical sources

Meenakshi Singh , Chetana Vaishnavi, Rakesh Kochhar

Department of Gastroenterology Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Background Clostridium difficile is the major etiological agent of nosocomial diarrhea primarily precipated by antimicrobial therapy.  Metronidazole and vancomycin are the first-line therapy for C. difficile infection (CDI), the epidemiology for susceptibility of which is not known. Moreover, the acquisition of resistance to clindamycin and fluoroquinolone is considered as one of the mechanisms whereby clonal strains emerge and predominate in healthcare environments.

Aim: The antibiogram profile of C. difficile isolated from clinical sources was investigated to check the resistance pattern for the above mentioned antibiotics.

Materials and Methods: Fecal samples obtained from 1,110 suspected cases of CDI were cultured on Columbia blood agar for isolation of C. difficile both by direct and by alcohol shock methods. Colonies suspected as those of C. difficile were identified by Gram staining, ultraviolet fluorescence, biochemical and molecular investigations. Antimicrobial susceptibility of C. difficile isolates was determined using the E-test for vancomycin, metronidazole, clindamycin and ciprofloxacin.

Results: The fecal samples belonged to 709 (63.9 %) males and 401 (36.1 %) females. The age of the patients ranged from 2 to 95 years with mean age of 38.7 years. C. difficile was isolated from 174 (15.7 %) of the total samples. Resistance was largely observed towards clindamycin (57.5 %) and ciprofloxacin (38.5 %) but significantly low towards metronidazole (1.72 %).  None of the isolates were resistant to vancomycin.

Conclusion: In our region, C. difficile with high degree of antibiotic resistance was found towards clindamycin and ciprofloxacin with low level of resistance to metronidazole and none towards vancomycin. Thus, antibiogram profiling of C. difficile will help to guide the clinicians for treatment options of patients with CDI.

M-04

Epidemiology of subacute intestinal obstruction

K Sunil Raviraj 1 , P T Chug 2 , V Singla 3 , P Sharma 3 , P Tyagi 3 , M Sachadeva 3 , A Kumar 3 , N Bansal, P Ranjan, K Mandhir , A K Arora

Department of Gastroenterology, Sir Ganga Ram Hospital, Old Rajender Nagar, Delhi 110 060, India

Introduction: Subacute intestinal obstruction (SAIO) is most common emergency in gastroenterology, can be due to strictures, adhesions or other lesions of any etiology.

Aim: To know the presentation, etiology and outcome of patients presenting with SAIO.

Materials and Methods: An observational study. A total of 136 subjects, presented with SAIO were included in the study. Abdominal radiographs, ultrasound and CT-scan were done and patients were managed according to the etiology. Subsequently analysis was made.

Results: Among 136 subjects 67.6 % (n=92) were male and 32.4 % (n=44) were female. Mean age of the subjects is 50.33 year (SD: 17.31). Median of duration of symptoms is 5 days. Period of hospitalization is 7.79+/-4.928 days. In 16.9 % (n=23) of subjects gave history of previous abdominal surgical procedures. Among radiological techniques, evidence of SAIO was found on X-ray in 94.9 % (n=129), on USG abdomen in 50 % (n=68) and on CT scan in 80.89 % (n=110. While 84.6 % (n=115) were improved with conservative measures, 13.2 % (n=18) were needed surgical management. Median day of surgery was 4th day after admission. While stricture was seen in 35.3 % (n=48), adhesions were identified in 28.67 % (n=39) and other lesions were identified in rest all subjects. Among etiologies, tuberculosis found in maximum number of patients (30.88 %, n=42) followed by malignancy (16.9 %, n=23), inflammatory bowel disease (2.9 %, n=4), ischemic bowel disease (2.2 %, n=3) and others in rest all patients. Ileum was involved in 75 % (n=102), jejunum in 63.2 % (n=86) and colon in 52.9 % (n=72). One patient died among all subjects (0.7 %).

M-05

Etiological profile of ascites at a tertiary care gastroenterology center

Eswar Moparty , P Shravan Kumar, M Umadevi, M Ramanna

Department of Gastroenterology, Gandhi Medical College, Hyderabad 500 025, India

Aim of the Study: To determine etiological profiles of patients presenting with ascites at Department of Gastroenterology, Gandhi Hospital.

Materials and Methods: All patients admitted with ascites in Gastroenterology Department between January and June 2014 (6 months) were included. History, clinical examination and relevant investigations were done; (ascitic fluid analysis including SAAG, HIV, HbsAg, HCV, serum creatine, USG abdomen). PT, 2D ECHO,TSH, FBS/ PPBS, HBA1c, ascitic fluid ADA, amylase, malignant cytology (cell block), TB PCR were done where necessary.

Results: Total number of patients were: 82 (males 58; females 24) cirrhosis: 60 (73.17 %) (alcohol - 40/ hep B - 7/ NASH - 5/cryptogenic - 4/hep C - 3/Wilson -1) pancreatic ascites: 9 (10.97 %) mixed ascites: 4 (cirrhosis + TB 1 ; + HCC 1; + metastases 1; + CKD 1) (4.87 %) malignancy: 3 (3.65 %) (colon - 1; ovarian - 1; GB - 1) Budd-Chiari: 2 (2.43 %) cardiac disease: 2 (2.43 %) tuberculosis: 1 (1.21 %) renal disease: 1 (1.21 %).

Conclusion: Cirrhosis accounted for majority (73.17 %) of ascites, pancreatic (10.97 %) and mixed ascites (4.87 %) accounted for a higher percentage than noted in literature. Among the cirrhotics, alcohol followed by hepatitis B accounts for majority of cases.

M-06

A retrospective study of colorectal neuroendocrine tumors

Srijan Mazumdar , Shaesta Mehta, Prachi S Patil

Department of Digestive Disease and Clinical Nutrition, Tata Memorial Hospital, Mumbai 400 012, India

Background: Neuroendocrine tumors (NET) are rare neoplasms comprising <0.5 % of all malignancies. The hindgut NETs are rarer and there is scarce data regarding these. We did a retrospective analysis of the characteristics of colorectal NETs (cNET).

Methods: Data was extracted from computerised hospital records of all patients attending the Gastroenterology OPD at Tata Memorial Hospital from 2005 - 2014 with diagnosis of cNET. We analyzed the demographic and clinical details.

Results: Thirty-seven patients with cNET were seen over 10 years. Twenty-two (61 %) were male. The mean age was 48 years (range 28-72). Commonest location was rectum in 30, appendix and cecum (3 each) and colon in 2 subjects. Common symptoms were pain (45 %), bleeding (30 %) and diarrhea (15 %). There were 11 well differentiated tumors, 1 moderately differentiated and 6 poorly differentiated tumors. The WHO Grade was: G1 in 9, G2 in 9 and G3 in 7 subjects. Twenty stained positive for chromogranin and synaptophysin while one was positive for NSE. Most patients had a normal CEA level. Chromogranin A levels were done in 5 subjects (median 437 U/L). Seventy-eight percent had metastatic disease with liver being the commonest site. Somatostatin receptor scans were done in 14 subjects with positive scan in 9. Forty percent subjects were treated by chemotherapy, 30 % by surgery, 15 % received octreotide analogues and 5 % by PRRT.

Conclusion: cNET are rare tumors and form a small percentage of colorectal tumors. Most patients had G1 or G2 tumors but metastatic disease at presentation. Surgery and chemotherapy were the common treatment modalities used.

M-07

Cigarette smoke condensate induced mRNAs gene expression of phospholipase A2 isoforms and their role in reactive oxygen species cascade in HCT-15 and HT-29 colon cells

Sanjeev K Shrama a , Gaurav Kaushik b , Chander Mohan Pathak a , Satyavati Rana a , Krishan Lal Khanduja a

aDepartment of Biophysics, and aGastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India, and bDepartment of Surgery, School of Medicine, K U Medical Center (KUMC), Kansas City, KS-66160, USA

Four different phospholipase A2 (PLA2) isoforms namely secretory phospholipase A2 (sPLA2), cytosolic phospholipase A2s (cPLA2), Ca2+independent phospholipase A2 (iPLA2) and platelet activating factor-acetyl hydrolase (PAF-AH) activated phospholipase A2, which are involved in remodeling of membrane phospholipids exist in the mammalian cells. Effects of cigarette smoke condensate (CSC) on cell viability, reactive oxygen species (ROS), mitochondrial reactive oxygen species (mtROS), superoxide radicals (SOR), mRNA expression (before and after knockdown of the specific phospholipase A2 groups with siRNA) were studied in HCT-15 and HT-29 cells. Cell survival decreased significantly after exposure with 50¼g CSC/mL in these cells. Total ROS, mtROS and SOR production were significantly increased in both cells after exposure with CSC. However, induction of ROS and SOR was more in HT-29 cells as compared to HCT-15 cells. Whereas, mtROS induction was found to be more in HCT-15 compare in HT-29 cells. The gene expression of phospholipase A2 groups such as IB, IID, III, IVA, IVB, IVC, VI, X, aiPLA2 and iPLA2 were expressed in HCT-15 cells. However in HT-29 cells, all these phospholipase A2 groups except IVC were observed. After exposure with cigarette smoke condensate, secretory phospholipase A2 IID group was upregulated significantly in HCT-15 cells only. HCT-15 cells transfected with IID siRNA did not respond to CSC in inducing reactive oxygen species, mitochondrial reactive oxygen species and superoxide radicals, and affecting viability. Therefore, it seems that particular phospholipase A2 mRNA of the specific cells are involved in controlling the cascades related to reactive oxygen species.

M-08

To study the spectrum of gastrointestinal and hepatopancreatobiliary tract malignancies at a tertiary centre in south India

Ramesh Kumar , Uday George Zachariah, C E Eapen, Ebby George Simon

Departments of Gastroenterology and Hepatology, Division of Gastrointestinal Sciences, Christian Medical College, Vellore 632 004, India

Background: Gastrointestinal (GI) and hepatopancreatobiliary tract malignancies are one of the major public health problems worldwide. There is paucity of data on current patterns of GI and HPB malignancies in India.

Materials and Methods: All patients seen in the outpatient/inpatient and endoscopy areas of the Departments of Gastroenterology and Hepatology with a diagnosis of a GI or HPB malignancy during the study period were enrolled after an informed consent. The diagnosis was based on the histopathological report of endoscopic biopsies in case of gastrointestinal cancers (esophageal/stomach and colorectal). A combination of radiological findings, laboratory markers and if available, histopathology were used to diagnose HPB malignancies. Data regarding clinical presentation, age distribution, site of involvement, life-style factors, socioeconomic status and histological types where available were collected and analyzed.

Result: Males were more frequently affected than females, M:F ratio was 1:0.6. Peak incidence was in 5th decade. Stomach was the commonest site (48.4 %) followed by esophagus (27.7 %), rectum (6.5 %), colon (5.0 %) and primary liver cancer (4.76 %). Majority of histological type was adenocarcinoma. Mean age for cancer of esophagus was 50.5 +/-11.4 year, stomach 54.8+/-12.9, colon 40.1+/-16.7, duodenum 40.3+/-11.4, pancreas 49.9+/-15.3 and HCC 55.5+/-12 years with an overall mean age of all GIM being 49.7+/-13.4 years. All malignancies were common in males except for cancer of gallbladder.

Conclusion: In the present study, stomach malignancies were the most common gastrointestinal malignancy.

M-09

Acute upper gastrointestinal bleeding in western India: Its characteristics, diagnoses and outcome

Sunil Pawar, Vinay Zanwar, Pravir Gambhire, Ashok Mohite, Ajay Choksey, Pravin Rathi

Department of Gastroenterology, Topiwala National Medical College and B Y L Nair Hospital, Mumbai Central, Mumbai 400 008, India

Background: Acute upper gastrointestinal (UGI) bleeding is a potentially life threatening condition requiring prompt and appropriate management.

Objective: To study clinical profile, etiology, endoscopic diagnosis and outcome of UGI bleeding at tertiary care centre.

Materials and Methods: This was prospective study. All patients presenting with UGI bleeding in the period between December 2013 to July 2014 were included.

Result: Total patients with UGI bleed were 217. Median age was 45 years. Twenty-one percent were females. Variceal bleeding was found in 46 % and nonvariceal in 35 %, 6 % had normal endoscopy and endoscopy could not be done in 13 % due to poor general condition. Most common etiology in variceal bleeding was alcoholic liver disease (56 %) followed by chronic liver disease (25 %), EHPVO (12 %) and NCPF (9 %). Most common etiology in nonvariceal group was esophagitis with pangastritis (28 %), antral ulcers (21 %), Mallory-Weiss and pangastritis (15 % each), esophageal ulcer (8 %), duodenal ulcer (5 %) and other causes in 6 %. In variceal group 16.6 % had history of NSAIDs or antiplatelet ingestion and in non variceal group 32 % had similar history. Mean Rockall and Blatchford score was 3 (SD 1.63) and 9 (SD 3.65) respectively while who required enodoscopic therapy were 3.6 and 10.7 respectively. Average time from hematemesis to hospital admission was 33 hours and from admission to endoscopy was 4 hours. Twenty-two percent required blood transfusion. Eight percent of patients died.

Conclusion: Common etiology was variceal bleed. NSAIDs were precipitating factor in both variceal and nonvariceal bleeding. Mean Rockall and Blatchford  score was 3 and 9 respectively.

M-10

Non-celiac gluten sensitivity: Exploring the new entity

Vinay Zanwar , Sunil Pawar , Ashok Mohite , Ravindra Surude, Qais Contractor¸ Pravin Rathi

Department of Gastroenterology, Topiwala National Medical College and B Y L Nair Hospital, Mumbai Central, Mumbai 400 008, India

Background: Spectrum of gluten-related disorders got a new entity, represented by gluten sensitivity. Clinical picture is a combination of irritable bowel syndrome (IBS) symptoms and systemic manifestations. No strict criteria for the diagnosis of non-celiac gluten sensitivity (NCGS) exist, prevalence claimed to be 6 %.

Aims and Objective: Study the existence and prevalence of NCGS.

Materials and Methods: Seventy patients between 18 to 65 yrs, with a diagnosis of IBS as per Rome III criteria, were included. Celiac disease and wheat allergy were excluded appropriately. Patients fulfilling the inclusion criteria were given gluten-free diet for 4 weeks and were followed weekly. The patients were interviewed for symptoms at baseline and weekly for 4 weeks; and compared on Visual Analogue Scale. Study population was given normal gluten containing diet to look for reappearance of the symptoms.

Results: On a visual analogue scale, 2 patients showed significant improvement with gluten-free diet for overall symptoms (p<0.05), pain (p<0.05), bloating p<0.05), satisfaction with stool consistency (p<0.05). On gluten rechallenge after completion of 4 weeks, patient symptom deterioration occurred in days to week duration.

Conclusions: Our data identifies a patient population suffering from non-celiac gluten sensitivity.

M-11

A case report of peritoneal mesothelioma -Rare variant

B Sajeeth Manikanda Prabu , K Muthukumaran, G Ramkumar, R Balamurali, T Rajkumar Solomon, A Murali, P Ganesh

Kilpauk Medical College, Chennai 600 010, India

Introduction: Primary peritoneal mesothelioma is a rare entity with an incidence of about 1-2 cases per million. It can occur in any age group, although the 50- to 69-year age group is the most affected. It is an unusual neoplasm in the sense that it demonstrates a wide spectrum of biological aggressiveness. The incidence has increased in the past two decades. Only 20 % to 33 % of all mesotheliomas arise from the peritoneum itself with pleura being the most common site of origin. Here we present a rare case of primary peritoneal mesothelioma-multi cystic variant.

Case Presentation: We report a case of middle aged gentleman who presented to our hospital with abdominal distension and pain. He had been having these complaints for two months and was variously diagnosed as hydatidosis, peritoneal secondaries etc. On examination he was found to have multiple abdominal hard lesions. Investigations including CECT abdomen, histopathology and immunohistochemistry (Ki and PCK- positive) clinched the diagnosis of malignant peritoneal mesothelioma. He was started on chemotherapy and has shown symptomatic response.

Conclusion: Malignant peritoneal mesothelioma is a rare fatal disorder but recent advances in chemotherapy have altered its prognosis. High index of suspicion is essential as histopathology alone helps in the diagnosis and early initiation of treatment is crucial for survival.

M-12

Effect of different proton pump inhibitors on antiplatelet function of clopidogrel in coronary artery disease patients

U Kumar , R Vijayvergiya * , S K Sinha ^ , V Dhawan # , N Berry ^ , R Kochhar ^

Departments of Internal Medicine, Cardiology*, Gastroenterology^ and Experimental Medicine#, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Introduction: Clopidogrel is a prodrug that has to be metabolized by cytochrome P450 in liver to generate the active metabolite. Proton pump inhibitors (PPI) are extensively metabolized by the same isoenzyme. Therefore, concerns exist that a pharmacological interaction.

Methods: Ninety patients who were diagnosed cases of CAD and were on Aspirin (150 mg PO daily) and clopidogrel (75 mg PO daily) but not on any PPI, were enrolled. Platelet aggregation test was done by ADP induced light transmission aggregometry method. Randomization was done by computer generated random numbers to include 30 patients in each PPI group. After 4-6 weeks of combined antiplatelet and PPI therapy, patients were followed up and platelet aggregation test was repeated. Change in parameter of platelet was compared with platelet function before introduction of PPIs.

Results: Study included 90 patients (72 males, age 55.0±9.5 years, BMI 25.7+3.46). Three groups did not differ with respect to age, gender, BMI and common risk factors for CAD. Platelet aggregation values at baseline and after PPI therapy in the three groups were as follows-esomeprazole 45.75+22.25 and 47.63+22.14; pantoprazole 42.50+22.14 and 35.03+18.40; and rabeprazole 45.30+29.46 and 38.30+26.06. There was no statistically significant difference in baseline and post PPI values in esomeprazole group (p value 0.09) but statistically significant difference was observed in baseline and post PPI values in both pantoprazole and rabeprazole groups (p value <0.001).

Conclusion: All three PPIs can be used in CAD patients on clopidogrel therapy but pantoprazole and rabeprazole should be preferred to esomeprazole.

M-13

ERCP- An audit

C Vijai Shankar , P Ratnakar Kini, Kani Shaikh Muhammed, K Prem Kumar, T Pugazhendhi, Mohammed Ali

Department of Medical Gastroenterology, Madras Medical College, Chennai 600 003, India

An audit of 358 ERCP’s done in our institution between January 2014 to August 2014. The common indications were choledocholithiasis accounting for 20 % (69 cases) followed by periampullary growth 13 % (48 cases), cholangitis 10 % (35 cases), hilar cholangiocarcinoma 7 % (26 cases), chronic pancreatitis 6.7 % (24 cases), postcholecystectomy biliary injury 6.1 % (22 cases) and acute pancreatitis 5 % (17 cases). Sphincterotomy and stenting was the common modality employed (61 %) for CBD stones. Balloon trawling attempted in 44 % of cases (30 cases) with 86 % success rate. Sludge and stone extraction was feasible in 41 % (28 cases). Of the periampullary growth, majority (61 %) were due to carcinoma of head of pancreas. Stenting was feasible with (38 %) or without biliary dilatation in 54 % of cases with hilar cholangiocarcinoma compared to 40 % in periampullary growth. In postcholecystectomy biliary strictures, leaks or residual stones our technical success rate was 73 %. Communicating pseudocyst of pancreas and ductal leak resulting in pancreatic ascites were stented with success rate of 82 % in those with successful cannulation (65 %) of pancreatic duct. Chronic pancreatitis with pancreatic stricture dilatation and stenting was feasible in only 22 % of cases. Overall technical success rate was 83 % and failures (17 %) were commonly encountered in those with periampullary lesions, chronic pancreatitis and those with altered upper gastrointestinal anatomy. Complications encountered were bleeding (0.8 %), pancreatitis (0.8 %) and perforation (0.55 %).

M-14

Learning curve of endoscopic sub-mucosal dissection - lessons learnt in a tertiary referral center from a non-endemic region for GI cancers

Amol Bapaye , N A Dubale

Department of Digestive Diseases and Endoscopy, Deenanath Mangeshkar Hospital and Research Center, Erandawne, Pune 411 004, India

Aims: Endoscopic sub-mucosal dissection (ESD) is fast replacing endoscopic mucosal resection (EMR) for mucosal and submucosal lesions. We evaluate the learning curve for ESD from a nonendemic region for GI cancers

Methods: Patients with mucosal/submucosal lesions diagnosed on endoscopy and radial EUS underwent ESD. Follow up endoscopy at 1, 3, 6 months.

Results: Duration: August 2010 to March 2013, N=33, M: F=25:8, mean age: 61.2 years (19–83). Locations of lesions: stomach–9, rectum–8, colon–10, esophagus–2, duodenum–4. Pathology: villous adenoma (VA)–19 (CA in situ–4), hamartomatous polyps–2, hyperplastic polyp–1, carcinoid–4, SMT–7. Enbloc resection in 72.7 %. Patients were divided in 2 groups (initial 20 and subsequent 13). Both groups were comparable for location, nature and mean size of lesions. In Gr. I, enbloc resection was successful in 65 % patients vs. 85 % in Gr. II. Mean procedure time was comparable in both groups – 81 min (30 – 150) and 82 min (25–150). Two in Gr. I had perforations, treated by clip** in one and surgery in other. Two underwent EFTR in Gr II, none in Gr I. Recurrence occurred in 20 % in Gr. 1 vs. 8 %, Gr. II–all post EPMR.

Conclusion: Sessile adenomas and SM lesions present opportunities to perform ESD in centers with low volumes of early cancers. We suggest a learning curve of minimum 20 ESD procedures in a low volume center to achieve reasonable proficiency.

M-15

Stress reduction by relaxation in Shavasan yogic posture (corpse position) during upper gastrointestinal endoscopy

M R Kotwal, C Z Rinchen

Sir Thutob Namgyal Memorial Hospital, Government of Sikkim, Gangtok, and www.shunyata.org

Introduction: Study was to examine the effects of Shavasan (A yogic posture for relaxation). Gastrointestinal endoscopy service requires a suitable ambient environment. Many patients fear GI endoscopy. Natural anxiety may be aggravated by horror stories from friends or inappropriate remarks by endoscopy staff. Yogic techniques in general and Shavasan in particular are known to improve psychosomatic health and enhance one’s ability to combat stressful situations.

Methods: This study was conducted on 63 consecutive patients undergoing endoscopy for various reasons. Patients were randomly assigned to two groups regardless of sex, age and underlying disease. Thirty-two patients relaxed in Shavasan before the procedure. Control group had 31 patients. Blood pressure, heart rate, and respiratory rate were recorded at the beginning and end of procedure. Perception of procedure using a 5 point attitude scale was assessed.

Results: Relaxation in Shavasan is effective in reducing stress during gastroscopic examination and any other medical situation. Statistically significant difference in systolic blood pressure, heart and respiratory rate was recorded in experimental (Shavasanic yogic group). Control group did not show any change in the parameters. Acceptance of procedure using a 5 point scale was more in the experimental group.

Conclusion: Preliminary study to see the effects in anxiety and stress in upper GI endoscopy subjects. Useful in disorders that generate anxiety and stress. Shavasan and its variations like deep breathing require further studies for evaluation of therapeutic effects in a wide range of functional disorders. Shavasan yoga a highly interesting field for further research.

M-16

Synchronous gastrointestinal malignancies- A case series

K Raja Yogesh , Mohammed Ali, T Pugazhendhi, Prem Kumar, Ratnakar Kini, Kani Shaikh

Madras Medical College, Chennai 600 003, India

The occurrence of multiple gastrointestinal cancers in the same patient was previously thought to be rare. Apart from it being a diagnostic oddity, the importance of a synchronous primary is that the diagnosis alters the prognosis and management of the patient considerably. In this case series, we report three cases of synchronous cancers, where both the first and the second primary cancers were found in the gastrointestinal tract.

Case 1: Sixty-five-year-old male presented to us with history of recurrent stale food vomiting and dysphagia. He was diagnosed to have synchronous esophageal and gastric cancers. The esophageal cancer was poorly differentiated squamous cell carcinoma and the gastric malignancy was a moderately differentiated adenocarcinoma.

Case 2: Seventy-year-old lady presented with symptoms of gastric outlet obstruction and dyschezia. She was found to have synchronous gastric and rectal cancer. The gastric cancer was a poorly differentiated adenocarcinoma and the rectal malignancy was a well differentiated adenocarcinoma. Patient had omental deposits at presentation.

Case 3: Fifty-nine-year-old male presenting with dysphagia, was found to have dual esophageal cancers. One lesion was well differentiated while the other was a poorly differentiated squamous cell carcinoma. Each of the cancers was symptomatic and in all three patients curative management was not possible, since the cancers were advanced. We suggest screening upper GI endoscopy in those with colorectal cancers and vice-versa, so that synchronous GI cancers can be diagnosed at an early stage, thereby making curative treatment options feasible.

M-17

An uncommon cause of melena

Prasad Bhate, Nirav Pipaliya , Dattatray Solanke, Meghraj Ingle, Aniruddha Phadke, Prabha Sawant

Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and Lokmanya Tilak Municipal General Hospital, Sion, Mumbai 400 022, India

We present a case of 52-year-old male, presented with multiple episodes of painless black tarry stools since 5 years and multiple episodes of self limited nasal bleeds before 10 years. Three years before admission, patient noted insidious onset, slowly progressive, painless, non-pulsatile, lump in upper abdomen. He had received over 50 blood transfusions during previous 5 years. Family history was not contributory. On examination he had tachycardia, postural hypotension, pallor and bilateral pedal edema and multiple telengiectatic lesions on finger pulp, buccal mucosa and on undersurface of tongue. Abdominal examination revealed 14 x 14 cm sized lump, continous with liver, a 4 cm splenomegaly and ascites. Investigations revealed microcytic, hypochromic anemia, hypoproteinemia, and normal AST/ALT. Ultrasonography showed hepatosplenomegaly with grossly enlarged left lobe, ascites and dilated portal vein. Upper GI endoscopy and colonoscopy revealed multiple telengiectatic lesions. CECT with CT angiography showed multiple telengiectasia in liver, spleen and pancreas with tortuous prominent hepatic artery and multiple hepatic arterioportal shunts leading to portal hypertension. Celiac angiography revealed the same findings. CT angiography of brain and lungs were normal. Diagnosis of hereditary hemorrhagic telengiectasia (HHT) was made on the basis of Curacao criteria. We treated the patient with argon plasma coagulation, hormonal therapy and he responded well to therapy. HHT or Osler-Weber-Rendu syndrome is a rare multisystemic vascular disorder with autosomal dominant inheritance. Recurrent GI bleeding occurs in 10 % to 40 % of patients and generally occurs in 5th decade of life.

M-18

Combination therapy of antitubercular drugs and endoscopic dilatation for gastroduodenal tuberculosis

Ashok Dalal , S Sachdeva, P Sakuja, A S Puri

G B Pant Hospital, J L Nehru Marg, New Delhi 110 002, India

Background/Aim: Gastroduodenal tuberculosis is an uncommon disease. Surgery has been considered as the SOC in most of the cases for both diagnosis and management. The aim of our study was to evaluate the efficacy of combination therapy of antitubercular therapy (ATT) with endoscopic dilatation as an alternative treatment for gastroduodenal tuberculosis.

Methods: Data of 34 cases of gastroduodenal tuberculosis presenting to us over last 5 years were analyzed. Patients were treated with 6-9 months of ATT and endoscopic dilatation and followed up for 1 year post therapy for endoscopic, radiological and symptomatic improvement.

Results: - Sixty-eight percent of the 34 patients were male with a mean age of 26.7 years. Most common presenting symptoms were vomiting and weight loss. Most common site of involvement was junction of D1 and D2. Tissue diagnosis was available in 28 patients. EMR for diagnosis was done in 7 patients, 5 of which had granuloma and 1 patient has AFB positivity. Median dilatation session required was 2. Mean duration of antitubercular therapy given was 8.5 months. Only one patient required surgery. Follow up data was available for 11 patients after 12 months and all were symptom free. Residual stricture size was measured using a 15 mm biliary balloon and 9 patient had stricture >15 mm and 2 patient have stricture between 10-15 mm.

Conclusion: Diagnosis of gastroduodenal tuberculosis can be made by endoscopic methods in majority of patients. Combination therapy of dilatation and ATT is an effective alternative to surgery and should be the SOC.

M-19

Corrosive injuries-Retrospective analysis and audit in tertiary care centre

N Thirumoorthi , R Kini, K Prem Kumar, Kani Sheikh, T Pugazhendhi, Mohammed Ali

Department of Medical Gastroenterology, Madras Medical College, Chennai 600 003, India

Background: The ingestion of corrosive substances induces a spectrum of injuries to the aero-digestive tract which includes extensive necrosis and perforation of the esophagus and stomach. The gold standard for safe assessment of the depth, extent of injury, and appropriate therapeutic regimen is upper GI scopy. The objective of this study is to report our clinical experience in adult patients diagnosed with corrosive ingestion and to evaluate the usage of Zargar 6-point OGD classification system of injury.

Methods: The study was a retrospective medical chart review of patients admitted following corrosive ingestion in Rajiv Gandhi Government General Hospital, Chennai between January 2007 to August 2014. The patients underwent OGD scopy within 72 hours of ingestion and mucosal damage was graded using Zargar's modified endoscopic classification system.

Results: Total of 844 patients were included for analysis, out of which 478 were females. Type of corrosive and quantity of ingestion was variable. All patients underwent OGD scopy within 72 hours of ingestion. Patients with severe grade of injuries (2b and above) were managed appropriately. Number of cases and grade of injury is shown in Table 1.

Table 1

Grade of injury

Esophagus

Stomach

Duodenum

No of cases

%

No of cases

%

No of cases

%

0

1

2a

2b

3a

3b

406

179

109

82

49

19

48.10

21.20

12.92

9.72

5.80

2.26

311

302

91

64

61

15

36.84

35.78

10.78

7.58

7.24

1.78

648

128

41

16

11

0

76.78

15.16

4.86

1.90

1.30

0

Total

844

100

844

100

844

100

Conclusion: Endoscopy following corrosive ingestion to assess mucosal injury is useful to determine the severity of injury. Incidence of Grade 2b and above injury is 19.9 % in this study, as they are the ones who need proper management and regular surveillance to prevent further complications.

M-20

Analysis of foreign bodies in the gastrointestinal tract

Ilavarasi, Kani Sheikh, Ratnakar Kini, K Premkumar, T Pugazhendhi, Mohammed Ali

Department of Medical Gastroenterology, Madras Medical College, Chennai 600 003, India

Introduction: Foreign body ingestion and food bolus impaction occur commonly and present various challenges to the gastroenterologist.

Objective and Methods: Prospective and retrospective analysis of 43 patients who had a foreign body in the gastrointestinal tract over a period of 4 years from August 2010–August 2014 in the Department of Medical Gastroenterology in Madras Medical College and Hospital. The type of foreign body most commonly encountered, the site of lodgement and management options were studied.

Results: Out of 43 patients, 21 were males and 22 were females. The most common foreign body encountered were food bolus impaction in 15 patients (34.9 %), followed by dentures in 8 (18.6 %), coins in 5 (11.6 %), blade, chain, jackfruit, EVL ligator hood, chemical bezoar, toothbrush, nails and pins. Three patients were schizophrenic patients out of which one patient had swallowed around 100 bell pins, a few of which entered the rectum and were removed by sigmoidoscopy. Four patients (9.3 %) had pre-existing pathological conditions (esophageal stricture). The most frequent site of impaction was the esophagus in 25 patients (58.1 %) followed by the stomach (30.2 %). The most common site of impaction in the esophagus was the proximal part. The instrument most commonly used to remove foreign body was rat tooth forceps. Endoscopic retrieval was feasible in 39 patients (88.3 %), remaining 4 patients were referred to the surgical gastroenterologists. Surgically managed patients included one with chemical bezoar in stomach (the part in the esophagus was removed endocopically), toothbrush, multiple iron nails and impacted pen cap. One patient managed endoscopically had hematoma following foreign body removal and managed by nasogastric tube insertion and proton pump inhibitors.

Conclusion: Foreign bodies in the gastrointestinal tract represents a challenging clinical situation and requires urgent intervention by the gastroenterologist.