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Occult hepatitis B virus infection in children born to HBsAg-positive mothers after neonatal passive-active immunoprophylaxis

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Abstract

Background

Occult hepatitis B virus infection (OBI) is a well-recognized clinical entity characterized by the detection of HBV DNA in serum and/or liver in the absence of detectable HBsAg. Diagnosis of OBI requires a sensitive HBV DNA assay.

Aim

We aimed at determining the frequency of OBI in infants, born to HBsAg-positive mothers, who received immunoprophylaxis at birth.

Methods

Sixty-four infants and children, born to HBsAg-positive mothers, who received hepatitis B immunoglobulin and HBV vaccine within 48 h after birth, were tested for HBV serological profile and HBV DNA by real-time PCR at least 1 month after last dose of HBV vaccine and not before 6 months of age.

Results

The median age of the studied infants and children was 8 months, ranging from 6 to 132 months; 54.7 % were females. HBV DNA was detected in 2 infants. One case had OBI; she was negative for HBsAg, anti-HBc total, HBeAg and was positive for anti-HBs (titer 267 mIU/mL) with low level of viremia (HBV DNA 1.13 x 103 IU/mL). Another infant showed immunoprophylaxis failure with positive HBsAg, anti-HBc total, HBeAg, negative anti-HBe and anti-HBs; HBV viral load was 1.7 × 108 IU/mL. Both mothers were HBsAg and HBeAg-positive.

Conclusion

OBI may occur in infants born to HBsAg-positive mothers despite the receipt of immunoprophylaxis. OBI was detected in a low frequency in the present study. Anti-HBs positivity does not exclude OBI.

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References

  1. Wiseman E, Fraser MA, Holden S, Glass A, Kidson BL, Heron LG, Maley MW, Ayres A, Locarnini SA, Levy MT. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust. 2009;190:489–92.

    PubMed  Google Scholar 

  2. Margolis HS, Coleman PJ, Brown RE, Mast EE, Sheingold SH, Arevalo JA. Prevention of hepatitis B virus transmission by immunization: an economic analysis of current recommendations. JAMA. 1995;274:1201–8.

    Article  CAS  PubMed  Google Scholar 

  3. Borgia G, Carleo MA, Gaeta GB, Gentile I. Hepatitis B in pregnancy. World J Gastroenterol. 2012;18:4677–83.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Piratvisuth T. Optimal management of HBV infection during pregnancy. Liver Int. 2013;1:188–94.

    Article  Google Scholar 

  5. Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, ​Moyer LA, Bell BP, Alter MJ. Advisory Committee on Immunization Practices (ACIP). A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54(RR-16):1–31.

  6. Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Brechot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult”? Hepatology. 2001;34:194–203.

    Article  CAS  PubMed  Google Scholar 

  7. Hollinger FB, Habibollahi P, Daneshmand A, Alavian SM. Occult hepatitis B infection in chronic hemodialysis patients: current concepts and strategy. Hepat Mon. 2010;10:199–204.

    Google Scholar 

  8. Hu KQ. Occult hepatitis B virus infection and its clinical implications. J Viral Hepat. 2002;9:243–57.

    Article  PubMed  Google Scholar 

  9. Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol. 2007;46:160–70.

    Article  PubMed  Google Scholar 

  10. van Hemert FJ, Zaaijer HL, Berkhout B, Lukashov VV. Occult hepatitis B infection: an evolutionary scenario. Virol J. 2008;5:146.

    Article  PubMed Central  PubMed  Google Scholar 

  11. El-Sherif A, Abou-Shady M, Abou-Zeid H, Elwassief A, Elbahrawy A, Ueda Y, Chiba T, Hosney AM. Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients. J Gastroenterol. 2009;44:359–64.

    Article  CAS  PubMed  Google Scholar 

  12. Datta S, Banerjee A, Chandra PK, Chowdhury A, Chakravarty R. Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers. J Med Virol. 2006;78:53–9.

    Article  PubMed  Google Scholar 

  13. Walz A, Wirth S, Hucke J, Gerner P. Vertical transmission of hepatitis B virus from mothers negative for HBV surface antigen and positive for antibody to HBV core antigen. J Infect Dis. 2009;200:1227–31.

    Article  PubMed  Google Scholar 

  14. Reesink HW, Engelfriet CP, Henn G, Mayr WR, Delage G, Bernier F, Krusius T, Assal A, Gallian P, Corbi C, Morel P, David B, De Micco P, Murokawa H, Yugi H, Hino S, Tadokoro K, Flesland O, Brojer E, Letowska M, Olim G, Nascimento F, Gonçalves H, Castro L, Morais M, Stezinar SL, Alvarez M, Sauleda S, González R, Niederhauser C, Stolz M, Allain JP, Owusu-Ofori S, Eglin R, Stramer S, Busch M, Strong DM, Epstein J, Biswas R. Occult hepatitis B infection in blood donors. Vox Sang. 2008;94:153–66.

    Article  CAS  PubMed  Google Scholar 

  15. Carman WF. The clinical significance of surface antigen variants of hepatitis B virus. J Viral Hepat. 1997;4:11–20.

    Article  PubMed  Google Scholar 

  16. Hamkar R, Aghakhani A, Soufian S, Banifazl M, Ghavami N, Nadri M, Sofian M, Ahmadi F, Razeghi E, Eslamifar A, Ramezani A. Surface gene mutations of hepatitis B virus among high-risk patients with occult hepatitis B virus infection. Diagn Microbiol Infect Dis. 2010;66:285–91.

    Article  CAS  PubMed  Google Scholar 

  17. 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. doi:10.1016/j.jhep.2012.02.010.

  18. Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, Rodewald LE, Douglas JM Jr, Janssen RS, Ward JW. Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55(RR-16):1–33. quiz CE1-4.

  19. Pollicino T, Raimondo G. Occult heaptitis B infection. J Hepatol. 2014;61:688–9.

    Article  PubMed  Google Scholar 

  20. Buchanan C, Tran TT. Management of chronic hepatitis B in pregnancy. Clin Liver Dis. 2010;14:495–504.

    Article  PubMed  Google Scholar 

  21. El-Karaksy HM, Mohsen LM, Saleh DA, Hamdy MS, Yassin NA, Farouk M, Salit ME, El-Shabrawi MH. Applicability and efficacy of a model for prevention of perinatal transmission of hepatitis B virus infection: single center study in Egypt. WJG. 2014;20(45):17075–83. doi:10.3748/wjg.v20.i45.17075.  

  22. Sun HY, Cheng CY, Lee NY, Yang CJ, Liang SH, Tsai MS, Ko WC, Liu WC, Wu PY, Wu CH, Lin HH, Hung CC. Seroprevalence of hepatitis B virus among adults at high risk for HIV transmission two decades after implementation of nationwide hepatitis B virus vaccination program in Taiwan. PLoS One. 2014;9:e90194.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Mu SC, Lin YM, Jow GM, Chen BF. Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan. J Hepatol. 2009;50:264–72.

    Article  CAS  PubMed  Google Scholar 

  24. Lu FM, Zhuang H. Management of hepatitis B in China. Chin Med J (Engl). 2009;122:3–4.

    Google Scholar 

  25. Su H, Zhang Y, Xu D, Wang B, Zhang L, Li D, **ao D, Li F, Zhang J, Yan Y. Occult hepatitis B virus infection in anti-HBs-positive infants born to HBsAg-positive mothers in China. PLoS One. 2013;8:e70768.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Meffre C, Le Strat Y, Delarocque-Astagneau E, Dubois F, Antona D, Lemasson JM, Warszawski J, Steinmetz J, Coste D, Meyer JF, Leiser S, Giordanella JP, Gueguen R, Desenclos JC. Prevalence of hepatitis B and hepatitis C virus infections in France in 2004: social factors are important predictors after adjusting for known risk factors. J Med Virol. 2010;82:546–55.

    Article  PubMed  Google Scholar 

  27. Chakvetadze C, Roussin C, Roux J, Mallet V, Petinelli ME, Pol S. Efficacy of hepatitis B sero-vaccination in newborns of African HBsAg positive mothers. Vaccine. 2011;29:2846–9.

    Article  PubMed  Google Scholar 

  28. Moezzi M, Imani R, Khosravi N, Pourheidar B, Ganji F, Karimi A. Hepatitis B seroprevalence and risk factors in adult population of Chaharmahal and Bakhtiari province in 2013. Hepat Mon. 2014;14:e17398.

    PubMed Central  PubMed  Google Scholar 

  29. Shahmoradi S, Yahyapour Y, Mahmoodi M, Alavian SM, Fazeli Z, Jazayeri SM. High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG. J Hepatol. 2012;57:515–21.

    Article  PubMed  Google Scholar 

  30. Lehman EM, Wilson ML. Epidemiology of hepatitis viruses among hepatocellular carcinoma cases and healthy people in Egypt: a systematic review and meta-analysis. Int J Cancer. 2009;124:690–7.

    Article  CAS  PubMed  Google Scholar 

  31. El-Zayadi A. Hepatitis B virus infection: the Egyptian situation. Arab J Gastroenterol. 2007;8:94–8.

    Google Scholar 

  32. Sayan M, Buğdacı MS. HBV vaccine escape mutations in a chronic hepatitis B patient treated with nucleos(t)ide analogues. Mikrobiyol Bul. 2013;47:544–9.

    Article  CAS  PubMed  Google Scholar 

  33. Mantovani N, Cicero M, Santana LC, Silveira C, do Carmo EP, Abrão PR, Diaz RS, Caseiro MM, Komninakis SV. Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil. Virol J. 2013;10:320. doi:10.1186/1743-422X-10-320.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Hollinger FB, Hepatitis B. Virus genetic diversity and its impact on diagnostic assays. J Viral Hepat. 2007;14:11–5.

    Article  PubMed  Google Scholar 

  35. El Chaar M, Candotti D, Crowther RA, Allain JP. Impact of hepatitis B virus surface protein mutations on the diagnosis of occult hepatitis B virus infection. Hepatology. 2010;52:1600–10.

    Article  PubMed  Google Scholar 

  36. Chen BF. Clinical significance of the hepatitis B virus pre-S deletion. FJJM. 2010;8:85–95.

    Google Scholar 

  37. Ayres A, Yuen L, Jackson KM, Manoharan S, Glass A, Maley M, Yoo W, Hong SP, Kim SO, Luciani F, Bowden DS, Bayliss J, Levy MT, Locarnini SA. Short duration of lamivudine for the prevention of hepatitis B virus transmission in pregnancy: lack of potency and selection of resistance mutations. J Viral Hepat. 2014;21:809–17.

    Article  CAS  PubMed  Google Scholar 

  38. Yin YZ, Zhou J, Zhang PZ, Hou HY. Identification of risk factors related to the failure of immunization to interrupt hepatitis B virus perinatal transmission. Zhonghua Gan Zang Bing Za Zhi. 2013;21:105–10.

    CAS  PubMed  Google Scholar 

  39. Kang W, Ding Z, Shen L, Zhao Z, Huang G, Zhang J, **ong Q, Zhang S, Zhang S, Wang F. Risk factors associated with immunoprophylaxis failure against mother to child transmission of hepatitis B virus and hepatitis B vaccination status in Yunnan province, China. Vaccine. 2014;32:3362–6.

    Article  PubMed  Google Scholar 

  40. Zhang L, Gui X, Wang B, Ji H, Yisilafu R, Li F, Zhou Y, Zhang L, Zhang H, Liu X. A study of immunoprophylaxis failure and risk factors of hepatitis B virus mother-to-infant transmission. Eur J Pediatr. 2014;173:1161–8.

    Article  CAS  PubMed  Google Scholar 

  41. Li T, Qiu JM, Miao MH, Su XJ, Duan T. Meta-analysis on the effect of hepatitis B immunoglobulin on blocking intrauterine infection of HBV during the third-trimester. **an Dai Fuke **zhan. 2009;18:197–200.

    CAS  Google Scholar 

  42. Shi Z, Li X, Ma L, Yang Y. Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to child transmission-a meta-analysis. Int J Infect Dis. 2010;14:e622–34.

    Article  PubMed  Google Scholar 

  43. Zhou YH, Hu YL. Effective strategy of prevent HBV mother to-child transmission. Zhonghua Erke Zazhi. 2010;13:273–6.

    Google Scholar 

  44. Gan L, Liu DY, Wei M. Mutations of hepatitis B virus S gene by hepatitis B immunoglobulin administration in late pregnancy. Afr J Microbio Res. 2012;6:5975–9.

    CAS  Google Scholar 

  45. El-Zayadi AR, Ibrahim EH, Badran HM, Saeid A, Moneib NA, Shemis MA, Abdel-Sattar RM, Ahmady AM, El-Nakeeb A. Anti-HBc screening in Egyptian blood donors reduces the risk of hepatitis B virus transmission. Transfus Med. 2008;18:55–61.

    Article  PubMed  Google Scholar 

  46. Ismail H, Soliman M, Ismail N. Occult hepatitis B virus infection in Egyptian hemodialysis patients with or without hepatitis C virus infection. Pathol Lab Med Int. 2010;2:113–20.

    Article  Google Scholar 

  47. Hassan ZK, Hafez MM, Mansor TM, Zekri AR. Occult HBV infection among Egyptian hepatocellular carcinoma patients. Virol J. 2011;8:90.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Ahmed A, Abdel Satar I, El Ahl H, Shousha W, Doss W. Occult hepatitis B in Egyptian thalassemic children. J Infect Dev Ctries. 2012;6:340–6.

    PubMed  Google Scholar 

  49. Centers for Disease Control and Prevention (CDC). Postvaccination serologic testing results for infants aged ≤24 months exposed to hepatitis B virus at birth: United States, 2008–2011.  MMWR Morb Mortal Wkly Rep. 2012;61:768–71.

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This work has been funded partially by the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.

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No conflict of interest to declare.

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Correspondence to Hanan Foaud.

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Foaud, H., Maklad, S., Mahmoud, F. et al. Occult hepatitis B virus infection in children born to HBsAg-positive mothers after neonatal passive-active immunoprophylaxis. Infection 43, 307–314 (2015). https://doi.org/10.1007/s15010-015-0733-6

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