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Clinical Implications and Management of Chronic Occult Hepatitis B Virus Infection

  • Hepatitis B (J Lim, Section Editor)
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Abstract

Purpose of Review

The purpose of this review is to discuss the clinical implications of occult hepatitis B virus infection (OBI) and management options.

Recent Findings

Data regarding the role of OBI as a co-infection and its ability to facility progression of cirrhosis and hepatocellular carcinoma remain conflicting. In a recent meta-analysis, those with chronic hepatitis C and occult hepatitis B co-infection were found to be at increased risk for development of hepatocellular carcinoma. There remains limited data on how to manage these patients to prevent disease progression.

Summary

OBI refers to the presence of hepatitis B viral (HBV) DNA in serum or hepatocytes in the absence of detectable HBV surface antigen (HBsAg) with or without serological markers of previous exposure. As our understanding of the virology has progressed, so has our understanding of the clinical implications of OBI. Despite the growing evidence of the clinical implications of OBI, there are also several conflicting reports in the literature. After years of research, we have further understanding of the pathogenesis of OBI, but many questions remain unanswered. What we do know is that what was once felt to be a relatively innocuous entity is now regarded as a clinically very relevant disease process requiring appropriate assessment and individualized clinical management.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30:2212–9.

    Article  CAS  PubMed  Google Scholar 

  2. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546–55.

    Article  PubMed  Google Scholar 

  3. Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008;49:652–7.

    Article  PubMed  Google Scholar 

  4. Mason AL, Xu L, Guo L, Kuhns M, Perrillo RP. Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen. Hepatology. 1998;27:1736–42.

    Article  CAS  PubMed  Google Scholar 

  5. Gerlich WH. Reduction of infectivity in chronic hepatitis B virus carriers among healthcare providers and pregnant women by antiviral therapy. Intervirology. 2014;57:202–11.

    Article  CAS  PubMed  Google Scholar 

  6. Stramer SL, Notari EP, Krysztof DE, Dodd RY. Hepatitis B virus testing by minipool nucleic acid testing: does it improve blood safety? Transfusion. 2013;53:2449–58.

    Article  CAS  PubMed  Google Scholar 

  7. Allain JP, Mihaljevic I, Gonzalez-Fraile MI, Gubbe K, Holm-Harritshøj L, Garcia JM, et al. Infectivity of blood products from donors with occult hepatitis B virus infection. Transfusion. 2013;53:1405–15.

    Article  PubMed  Google Scholar 

  8. Coppola N, Loquercio G, Tonziello G, Azzaro R, Pisaturo M. HBV transmission from an occult carrier with five mutations the major hydrophilic region of HBsAg to an immunosuppressed plasma recipient. J Clin Virol. 2013;58:315–7.

    Article  CAS  PubMed  Google Scholar 

  9. Furuta RA, Kondo Y, Saito T, Tomita M, Oka K, Kishimoto Y. Transfusions of red blood cells from an occult hepatitis B virus carrier without apparent signs of transfusion-transmitted hepatitis B infection. Transfus Med. 2008;18:379–81.

    Article  CAS  PubMed  Google Scholar 

  10. Su TH, Chen PJ, Chen TC, Cheng HR, Li L, Lin KS, et al. The clinical significance of occult hepatitis B transfusion in Taiwan—a look-back study. Transfus Med. 2011;21:33–41.

    Article  PubMed  Google Scholar 

  11. Seo DH, Whang DH, Song EY, Han KS. Occult hepatitis B virus infection and blood transfusion. World J Hepatol. 2015;7:600–6.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Fontenele AM, Filho NS, Ferreira AS. Occult hepatitis B in patients on hemodialysis: a review. Ann Hepatol. 2013;12:527–31.

    PubMed  Google Scholar 

  13. Minuk GY, Sun DF, Greenberg R, Zhang M, Hawkins K. Occult hepatitis B virus infection in a North American adult hemodialysis patient population. Hepatology. 2004;40:1072–7.

    Article  CAS  PubMed  Google Scholar 

  14. Yoo JH, Hwang SG, Yang DH, Son MS, Kwon CI, Ko KH. Prevalence of occult hepatitis B virus infection in hemodialysis patients. Korean J Gastroenterol. 2013;61:209–14.

    Article  PubMed  Google Scholar 

  15. Wong PN, Fung TT, Mak SK, Lo KY, Tong GM, Wong Y, et al. Hepatitis B virus infection in dialysis patients. J Gastroenterol Hepatol. 2005;20:1641–51.

    Article  PubMed  Google Scholar 

  16. Fabrizi F, Messa P, Martin P. Hepatitis B virus infection and the dialysis patient. Semin Dial. 2008;21:440–6.

    Article  PubMed  Google Scholar 

  17. Centers for Disease Control and Prevention (CDC). Hepatitis-control measures for hepatitis B in dialysis centers. In: Hepatitis surveillance report no. 41. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, CDC; 1977:12–17.

  18. Moyer LA, Alter MJ, Favero MS. Hemodialysis-associated hepatitis B; revised recommendations for serologic screening. Semin Dial. 1990;3:201–4.

    Article  Google Scholar 

  19. Raimondo G, Caccamo G, Filomia R, Pollicino T. Occult HBV infection. Semin Immunopathol. 2013;35:39–52.

    Article  CAS  PubMed  Google Scholar 

  20. Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando ME, Raimondo G. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med. 1999;341:22–6.

    Article  CAS  PubMed  Google Scholar 

  21. Samuel D, Forns X, Berenguer M, Trautwein C, Burroughs A, Rizzetto M, et al. Report of the monothematic EASL conference on liver transplantation for viral hepatitis (Paris, France, January 12-14, 2006). J Hepatol. 2006;45:127–43.

    Article  PubMed  Google Scholar 

  22. Chazouillères O, Mamish D, Kim M, Carey K, Ferrell L, Roberts JP, et al. “Occult” hepatitis B virus as source of infection in liver transplant recipients. Lancet. 1994;343:142–6.

    Article  PubMed  Google Scholar 

  23. Dickson RC, Everhart JE, Lake JR, Wei Y, Seaberg EC, Wiesner RH, et al. Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. Gastroenterology. 1997;113:1668–74.

    Article  CAS  PubMed  Google Scholar 

  24. Chang MS, Olsen SK, Pichardo EM, Stiles JB, Rosenthal-Cogan L, Brubaker WD, et al. Prevention of de novo hepatitis B in recipients of core antibody-positive livers with lamivudine and other nucleos(t)ides: a 12-year experience. Transplantation. 2013;95:960–5.

    Article  CAS  PubMed  Google Scholar 

  25. Song ZL, Chi YJ, Zhen WP, Teng DH, Zheng H. Application of nucleoside analogues to liver transplant recipients with hepatitis B. World J Gastroenterol. 2015;21:12091–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kwon CI, Hwang SG, Shin SJ, Chang SW, Kim SY, Ko KH, et al. Occult hepatitis B virus infection in pregnant woman and its clinical implication. Liver Int. 2008;28:667–74.

    Article  CAS  PubMed  Google Scholar 

  27. Maldonado-Rodriguez A, Cevallos AM, Rojas-Montes O, Enriquez-Navarro K, Alvarez-Muñoz MT, Lira R. Occult hepatitis B virus co-infection in human immunodeficiency virus-positive patients: a review of prevalence, diagnosis and clinical significance. World J Hepatol. 2015;7:253–60.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Filippini P, Coppola N, Pisapia R, Scolastico C, Marrocco C, Zaccariello A, et al. Impact of occult hepatitis B virus infection in HIV patients naive for antiretroviral therapy. AIDS. 2006;20:1253–60.

    Article  PubMed  Google Scholar 

  29. • Sagnelli E, Pisaturo M, Martini S, Filippini P, Sagnelli C, Coppola N. Clinical impact of occult hepatitis B virus infection in immunosuppressed patients. World J Hepatol. 2014;6:384–93. Important review about immunosuppressed patients with occult hepatitis B infection.

  30. Coppola N, Onorato L, Pisaturo M, Macera M, Sagnelli C, Martini S, et al. Role of occult hepatitis B virus infection in chronic hepatitis C. World J Gastroenterol. 2015;21:11931–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Squadrito G, Cacciola I, Alibrandi A, Pollicino T, Raimondo G. Impact of occult hepatitis B virus infection on the outcome of chronic hepatitis C. J Hepatol. 2013;59:696–700.

    Article  PubMed  Google Scholar 

  32. Sagnelli E, Imparato M, Coppola N, Pisapia R, Sagnelli C, Messina V, et al. Diagnosis and clinical impact of occult hepatitis B infection in patients with biopsy proven chronic hepatitis C: a multicenter study. J Med Virol. 2008;80:1547–53.

    Article  CAS  PubMed  Google Scholar 

  33. Covolo L, Pollicino T, Raimondo G, Donato F. Occult hepatitis B virus and the risk for chronic liver disease: a meta-analysis. Dig Liver Dis. 2013;45:238–44. Recent meta-analysis of risk for progression to cirrhosis in those with occult hepatitis B.

    Article  PubMed  Google Scholar 

  34. •• Pollicino T, Squadrito G, Cerenzia G, Cacciola I, Raffa G, Craxi A, Farinati F, Missale G, Smedile A, Tiribelli C, Villa E, Raimondo G. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology. 2004;126(1):102–10.

  35. Squadrito G, Pollicino T, Cacciola I, Caccamo G, Villari D, La Masa T, et al. Occult hepatitis B virus infection is associated with the development of hepatocellular carcinoma in chronic hepatitis C patients. Cancer. 2006;106:1326–30.

    Article  PubMed  Google Scholar 

  36. Obika M, Shinji T, Fujioka S, Terada R, Ryuko H, Lwin AA, et al. Hepatitis B virus DNA in liver tissue and risk for hepatocarcinogenesis in patients with hepatitis C virus-related chronic liver disease. A prospective study. Intervirology. 2008;51:59–68.

    Article  CAS  PubMed  Google Scholar 

  37. Shetty K, Hussain M, Nei L, Reddy KR, Lok AS. Prevalence and significance of occult hepatitis B in a liver transplant population with chronic hepatitis C. Liver Transpl. 2008;14:534–40.

    Article  PubMed  Google Scholar 

  38. Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, Hussain M, Morgan TR. Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in United States patients with chronic hepatitis C. Hepatology. 2011;54:434–42.

    Article  PubMed  PubMed Central  Google Scholar 

  39. •• Shi Y, Wu YH, Wu W, Zhang WJ, Yang J, Chen Z. Association between occult hepatitis B infection and the risk of hepatocellular carcinoma: a meta-analysis. Liver Int. 2012;32:231–40. Recent meta-analysis of risk of development of HCC in those with occult hepatitis B.

  40. Kim CM, Koike K, Saito I, Miyamura T, Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature. 1991;351:317–20.

    Article  CAS  PubMed  Google Scholar 

  41. Tamori A, Yamanishi Y, Kawashima S, Kanehisa M, Enomoto M, Tanaka H, et al. Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA. Clin Cancer Res. 2005;11:5821–6.

    Article  CAS  PubMed  Google Scholar 

  42. Pollicino T, Saitta C, Raimondo G. Hepatocellular carcinoma: the point of view of the hepatitis B virus. Carcinogeneis. 2011;32:1122–32.

    Article  CAS  Google Scholar 

  43. Tan YJ. Hepatitis B virus infection and the risk of hepatocellular carcinoma. World J Gastroenterol. 2011;17:4853–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fallot G, Neuveut C, Buendia MA. Diverse roles of hepatitis B virus in liver cancer. Curr Opin Virol. 2012;2:467–73.

    Article  CAS  PubMed  Google Scholar 

  45. Samal J, Kandpal M, Vivekanandan P. Molecular mechanisms underlying occult hepatitis B virus infection. Clin Microbiol Rev. 2012;25:142–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Matsuoka S, Nirei K, Tamura A, Nakamura H, Matsumura H, Oshiro S, et al. Influence of occult hepatitis B virus coinfection on the incidence of fibrosis and hepatocellular carcinoma in chronic hepatitis C. Intervirology. 2008;51:352–61.

    Article  CAS  PubMed  Google Scholar 

  47. Arababadi MK, Nasiri Ahmadabadi B, Kennedy D. Current information on the immunologic status of occult hepatitis B infection. Transfusion. 2012;52:1819–26.

    Article  CAS  PubMed  Google Scholar 

  48. Werle-Lapostolle B, Bowden S, Locarnini S, Wursthorn K, Petersen J, Lau G, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology. 2004;126:1750–8.

    Article  CAS  PubMed  Google Scholar 

  49. Wong DK, Huang FY, Lai CL, Poon RT, Seto WK, Fung J, et al. Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma. Hepatology. 2011;54:829–36.

    Article  CAS  PubMed  Google Scholar 

  50. Wong DK, Yuen MF, Poon RT, Yuen JC, Fung J, Lai CL. Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma. J Hepatol. 2006;45:553–9.

    Article  CAS  PubMed  Google Scholar 

  51. Paterlini P, Poussin K, Kew M, Franco D, Brechot C. Selective accumulation of the X transcript of hepatitis B virus in patients negative for hepatitis B surface antigen with hepatocellular carcinoma. Hepatology. 1995;21:313–21.

    CAS  PubMed  Google Scholar 

  52. Gozuacik D, Murakami Y, Saigo K, Chami M, Mugnier C, Lagorce D, et al. Identification of human cancer-related genes by naturally occurring hepatitis B virus DNA tagging. Oncogene. 2001;20:6233–40.

    Article  CAS  PubMed  Google Scholar 

  53. Bläckberg J, Kidd-Ljunggren K. Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation. J Hepatol. 2000;33:992–7.

    Article  PubMed  Google Scholar 

  54. Yuki N, Nagaoka T, Yamashiro M, Mochizuki K, Kaneko A, Yamamoto K, et al. Long-term histologic and virologic outcomes of acute self-limited hepatitis B. Hepatology. 2003;37:1172–9.

    Article  CAS  PubMed  Google Scholar 

  55. Pollicino T, Saitta C. Occult hepatitis B virus and hepatocellular carcinoma. World J Gastroenterol. 2014;20:5951–61.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagie JH, Pucino F, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148:519–28.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Jang JW, Choi JY, Bae SH, Yoon SK, Chang UI, Kim CW, et al. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization. Hepatology. 2006;43:233–40.

    Article  CAS  PubMed  Google Scholar 

  58. Lau GK, Yiu HH, Fong DY, Cheng HC, Au WY, Lai LS, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology. 2003;125:1742–9.

    Article  CAS  PubMed  Google Scholar 

  59. Ahmed A, Keeffe EB. Lamivudine therapy for chemotherapy-induced reactivation of hepatitis B virus infection. Am J Gastroenterol. 1999;94:249–51.

    Article  CAS  PubMed  Google Scholar 

  60. Dai MS, Wu PF, Lu JJ, Shyu RY, Chao TY. Preemptive use of lamivudine in breast cancer patients carrying hepatitis B virus undergoing cytotoxic chemotherapy: a longitudinal study. Support Care Cancer. 2004;12:191–6.

    Article  PubMed  Google Scholar 

  61. Leaw SJ, Yen CJ, Huang WT, Chen TY, Su CW, Tsao CJ. Preemptive use of interferon or lamivudine for hepatitis B reactivation in patients with aggressive lymphoma receiving chemotherapy. Ann Hematol. 2004;83:270–5.

    Article  CAS  PubMed  Google Scholar 

  62. Nagamatsu H, Itano S, Nagaoka S, Akiyoshi J, Matsugaki S, Kurogi J, et al. Prophylactic lamivudine administration prevents exacerbation of liver damage in HBe antigen positive patients with hepatocellular carcinoma undergoing transhepatic arterial infusion chemotherapy. Am J Gastroenterol. 2004;99:2369–75.

    Article  CAS  PubMed  Google Scholar 

  63. Rossi G, Pelizzari A, Motta M, Puoti M. Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy. Br J Haematol. 2001;115:58–62.

    Article  CAS  PubMed  Google Scholar 

  64. Yeo W, Ho WM, Hui P, Chan PK, Lam KC, Lee JJ, et al. Use of lamivudine to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patients. Breast Cancer Res Treat. 2004;88:209–15.

    Article  CAS  PubMed  Google Scholar 

  65. Li YH, He YF, Jiang WQ, Wang FH, Lin HX, Zhang L, et al. Lamivudine prophylaxis reduces the incidence and severity of hepatitis in hepatitis B virus carriers who receive chemotherapy for lymphoma. Cancer. 2006;106:1320–5.

    Article  CAS  PubMed  Google Scholar 

  66. Kohrt HE, Ouyang DL, Keeffe EB. Systematic review: lamivudine prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection. Aliment Pharmacol Ther. 2006;24:1003–16.

    Article  CAS  PubMed  Google Scholar 

  67. Yeo W, Chan PK, Ho WM, Zee B, Lam KC, Lei KI, et al. Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy. J Clin Oncol. 2004;22:927–34.

    Article  CAS  PubMed  Google Scholar 

  68. Saab S, Dong MH, Joseph TA, Tong MJ. Hepatitis B prophylaxis in patients undergoing chemotherapy for lymphoma: a decision analysis model. Hepatology. 2007;46:1049–56.

    Article  CAS  PubMed  Google Scholar 

  69. Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin’s lymphoma: a randomized trial. Hepatology. 2008;47:844–53.

    Article  CAS  PubMed  Google Scholar 

  70. Pelizzari AM, Motta M, Cariani E, Turconi P, Borlenghi E, Rossi G. Frequency of hepatitis B virus mutant in asymptomatic hepatitis B virus carriers receiving prophylactic lamivudine during chemotherapy for hematologic malignancies. Hematol J. 2004;5:325–8.

    Article  CAS  PubMed  Google Scholar 

  71. Mastroianni CM, Lichtner M, Citton R, Del Borgo C, Rago A, Martini H, et al. Current trends in management of hepatitis B virus reactivation in the biologic therapy era. World J Gastroenterol. 2011;17:3881–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Paul S, Saxena A, Terrin N, Viveiros K, Balk EM, Wong JB. Hepatitis B virus reactivation and prophylaxis during solid tumor chemotherapy: a systematic review and meta-analysis. Ann Intern Med. 2016;164:30–40.

    Article  PubMed  Google Scholar 

  73. Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27:605–11.

    Article  CAS  PubMed  Google Scholar 

  74. Coppola N, Tonziello G, Pisaturo M, Messina V, Guastafierro S, Fiore M, et al. Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings. J Med Virol. 2011;83:1909–16.

    Article  PubMed  Google Scholar 

  75. Yeo W, Johnson PJ. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology. 2006;43:209–20.

    Article  CAS  PubMed  Google Scholar 

  76. Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol. 2007;136:699–712.

    Article  CAS  PubMed  Google Scholar 

  77. Kusumoto S, Tanaka Y, Mizokami M, Ueda R. Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma. Int J Hematol. 2009;90:13–23.

    Article  CAS  PubMed  Google Scholar 

  78. Ustün C, Koç H, Karayalcin S, Akyol G, Gürman G, Ilhan O, et al. Hepatitis B virus infection in allogeneic bone marrow transplantation. Bone Marrow Transplant. 1997;20:289–96.

    Article  PubMed  Google Scholar 

  79. Lau GK, Leung YH, Fong DY, Au WY, Kwong YL, Lie A, et al. High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation. Blood. 2002;99:2324–30.

    Article  CAS  PubMed  Google Scholar 

  80. Ma SY, Lau GK, Cheng VC, Liang R. Hepatitis B reactivation in patients positive for hepatitis B surface antigen undergoing autologous hematopoietic cell transplantation. Leuk Lymphoma. 2003;44:1281–5.

    Article  CAS  PubMed  Google Scholar 

  81. Knöll A, Boehm S, Hahn J, Holler E, Jilg W. Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant. 2004;33:925–9.

    Article  PubMed  Google Scholar 

  82. Hui CK, Sun J, Au WY, Lie AK, Yueng YH, Zhang HY, et al. Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol. 2005;42:813–9.

    Article  CAS  PubMed  Google Scholar 

  83. Michel M, Duvoux C, Hezode C, Cherqui D. Hepatitis after infliximab in a patient with hepatitis B virus treated for an adult onset still’s disease. J Rheumatol. 2003;30:1624–5.

    PubMed  Google Scholar 

  84. Ostuni P, Botsios C, Punzi L, Sfriso P, Todesco S. Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with rheumatoid arthritis treated with infliximab and low dose methotrexate. Ann Rheum Dis. 2003;62:686–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Lee YH, Bae SC, Song GG. Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Clin Exp Rheumatol. 2013;31:118–21.

    PubMed  Google Scholar 

  86. Ryu HH, Lee EY, Shin K, Choi IA, Lee YJ, Yoo B, et al. Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNFα agents: a retrospective analysis of 49 cases. Clin Rheumatol. 2012;31:931–6.

    Article  PubMed  Google Scholar 

  87. Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F, Lopez-Roses L, Brito-Zerón P, Pérez-de-Lis M, BIOGEAS Study Group, et al. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore). 2011;90:359–71.

    Article  Google Scholar 

  88. Squadrito G, Spinella R, Raimondo G. The clinical significance of occult HBV infection. Ann Gastroenterol. 2014;27:15–9.

    PubMed  PubMed Central  Google Scholar 

  89. Pei SN, Chen CH, Lee CM, Wang MC, Ma MC, Hu TH, et al. Reactivation of hepatitis B virus following rituximab based regimens: a serious complication in both HBsAg positive and HBsAg-negative patients. Ann Hematol. 2010;89:255–62.

    Article  CAS  PubMed  Google Scholar 

  90. European Association For The Study Of The Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.

    Article  Google Scholar 

  91. Tuna N, Karabay O. Hepatitis B reactivation and timing for prophylaxis. World J Gastroenterol. 2015;21:2263–4.

    PubMed  PubMed Central  Google Scholar 

  92. Abramson JS, Chung RT. Optimal antiviral prophylaxis against hepatitis B reactivation in patients receiving rituximab-based chemotherapy for lymphoma. JAMA. 2014;312:2505–7.

    Article  CAS  PubMed  Google Scholar 

  93. Brost S, Schnitzler P, Stremmel W, Eisenbach C. Entecavir as treatment for reactivation of hepatitis B in immunosuppressed patients. World J Gastroenterol. 2010;16:5447–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Chemin I, Guillaud O, Queyron PC, Trépo C. Close monitoring of serum HBV DNA levels and liver enzymes levels is most useful in the management of patients with occult HBV infection. J Hepatol. 2009;51:824–5.

    Article  CAS  PubMed  Google Scholar 

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  1. Division of Gastroenterology and Hepatology, School of Medicine, University of California Irvine, Orange, CA, 92868, USA

    Mohit Mittal & Ke-Qin Hu

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Mittal, M., Hu, KQ. Clinical Implications and Management of Chronic Occult Hepatitis B Virus Infection. Curr Hepatology Rep 16, 90–96 (2017). https://doi.org/10.1007/s11901-017-0339-9

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