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Management of hepatitis B during pregnancy

Nature Reviews Gastroenterology & Hepatology volume 11, pages 402–409 (2014)Cite this article

Subjects

Key Points

  • Perinatal transmission of hepatitis B still occurs worldwide despite the availability of appropriate vaccination

  • High maternal HBV viraemia (>107 copies per ml) is recognized as a risk factor for immunoprophylaxis failure

  • Stratifying the two separate issues of maternal liver disease versus HBV mother-to-child transmission (MTCT) is crucial for clinical decision-making regarding treatment

  • Treatment of confirmed high maternal HBV viraemia in the third trimester might be warranted to reduce the risk of MTCT

Abstract

Chronic HBV infection is estimated to affect >350 million people worldwide and represents a substantial source of morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Mother-to-child transmission (MTCT) remains an important source of incident cases of hepatitis B. Immunoprophylaxis of infants born to mothers who are positive for hepatitis B surface antigen is used to prevent MTCT; however, under-utilization of this intervention in certain regions endemic for HBV infection and failure of immunoprophylaxis in 5–10% of cases are barriers to preventing HBV transmission via this route. Data suggest that a high level of HBV viraemia in pregnant women is a substantial risk factor for immunoprophylaxis failure. Potential means of reducing viral load include antiviral therapy in the third trimester to reduce exposure of the neonate to the virus. Determining the optimal time to treat active HBV-related liver disease in women who wish to become pregnant, as well as managing antiviral therapy in patients who become pregnant, remains challenging. Owing to the vulnerable population affected by these issues, clinical trials are difficult and, thus, evidence-based recommendations are limited. Emerging data are addressing management of HBV during pregnancy that health-care providers should be made aware of. Here, we provide an overview of issues pertinent to HBV infection during pregnancy and present a management algorithm.

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Figure 1: Immunoprophylaxis failure rate for HBsAg-positive women according to HBV DNA threshold.

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References

  1. Bosch, F. X. et al. Epidemiology of hepatocellular carcinoma. Clinic Liver Dis. 9, 191–211 (2005).

    Article  Google Scholar 

  2. WHO Fact Sheets. Hepatitis B [online], (2000).

  3. Kowdley, K. V. et al. Prevalence of chronic hepatitis B among foreign born persons living in the United States by country of origin. Hepatology 56, 422–433 (2012).

    Article  Google Scholar 

  4. Devaki, P. et al. Changes in hepatitis B (HBV) vaccination rates and differences in various general demographics across National Health and Nutrition Examination Surveys (NHANES) from 1999–2010. Hepatology 58 (Suppl.), 607A–608A (2013).

    Google Scholar 

  5. Stevens, C. E. et al. HBeAg and anti-HBe detection by radioimmunoassay: correlation with vertical transmission of hepatitis B virus in Taiwan. J. Med. Virol. 3, 237–241 (1979).

    Article  CAS  Google Scholar 

  6. Edmunds, W. J. et al. The influence of age on the development of the hepatitis B carrier state. Proc. R. Soc. B. 253, 197–201 (1993).

    Article  CAS  Google Scholar 

  7. US Department of Health and Human Services. MMWR: a comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States [online], (2005).

  8. Pan, C. Q. et al. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B. Clin. Gastroenterol. Hepatol. 10, 452–459 (2012).

    Article  Google Scholar 

  9. Stevens, C. E. et al. Vertical transmission of hepatitis B antigen in Taiwan. N. Engl. J. Med. 292, 771–774 (1975).

    Article  CAS  Google Scholar 

  10. Ghaziasadi, A. et al. Mutational analysis of HBsAg-positive mothers and their infected children despite immunoprophylaxis. Iran J. Allergy Asthma Immunol. 12, 352–360 (2013).

    CAS  PubMed  Google Scholar 

  11. Lee, S. D. et al. Maternal hepatitis B virus DNA in mother-infant transmission. Lancet 1, 719 (1989).

    Article  CAS  Google Scholar 

  12. Ngui, S. L. et al. Low detection rate and maternal provenance of hepatitis B virus S gene mutants in cases of failed postnatal immunoprophylaxis in England and Wales. J. Infect. Dis. 176, 1360–1365 (1997).

    Article  CAS  Google Scholar 

  13. Karthigesu, V. D. et al. A hepatitis B virus variant found in the sera of immunised children induces a conformational change in the HBsAg “a” determinant. J. Med. Virol. 58, 346–352 (1999).

    Article  CAS  Google Scholar 

  14. Chiang, C. J. et al. Thirty-year outcomes of the National Hepatitis B Immunization Program in Taiwan. JAMA 310, 974–976 (2013).

    Article  CAS  Google Scholar 

  15. US Preventive Services Task Force. Screening for hepatitis B virus infection in pregnancy: US Preventive Services Task Force reaffirmation recommendation statement. Ann. Intern. Med. 150, 869–873 (2009).

  16. Lok, A. S. & McMahon, B. J. AASLD practice guideline update chronic hepatitis B: update 2009. Hepatology 50, 1–36 (2009).

    Google Scholar 

  17. Bai, G. Q., Li, S. H., Yue, Y. F. & Shi, L. The study on role of peripheral blood mononuclear cell in HBV intrauterine infection. Arch. Gynecol. Obstet. 283, 317–321 (2011).

    Article  CAS  Google Scholar 

  18. Yu, M. et al. Correlation between vertical transmission of hepatitis B virus and the expression of HBsAg in ovarian follicles and placenta. PLoS ONE 8, e5426 (2013).

    Article  Google Scholar 

  19. Lin, H. H. et al. Transplacental leakage of HBeAg-positive maternal blood as the most likely route in causing intrauterine infection with hepatitis B virus. J. Pediatr. 111, 877–881 (1987).

    Article  CAS  Google Scholar 

  20. Lazizi, Y., Badur, S. & Perk, Y. Selective unresponsiveness to HBsAg vaccine in newborns related with an in utero passage of hepatitis B virus DNA. Vaccine 15, 1095–1100 (1997).

    Article  CAS  Google Scholar 

  21. Zhang, S. L. et al. Mechanism of Intrauterine infection of hepatitis B virus. World J. Gastroenterology 10, 437–438 (2004).

    Article  CAS  Google Scholar 

  22. Xu, D. Z. et al. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case–control study. J. Med. Virol. 67, 20–26 (2002).

    Article  Google Scholar 

  23. Towers, C. V., Asrat, T. & Rumney, P. The presence of hepatitis B surface antigen and deoxyribonucleic acid in amniotic fluid and cord blood. Am. J. Obstet. Gynecol. 184, 1514–1518 (2001).

    Article  CAS  Google Scholar 

  24. Yi, W. et al. Risk of hepatitis B virus vertical transmission after amniocentesis in mothers with chronic hepatitis B. J. Hepatol. http://dx.doi.org/10.1016/j.jhep.2013.11.008.

  25. Wong, V. C., Lee, A. K. & Ip, H. M. Transmission of hepatitis B antigens from symptoms free carrier mothers to the fetus and the infant. Br. J. Obstet. Gynaecol. 87, 958–965 (1980).

    Article  CAS  Google Scholar 

  26. Hill, J. B. et al. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet. Gynecol. 99, 1049–1052 (2002).

    PubMed  Google Scholar 

  27. Mirochnik, M. et al. Antiretrovial concentrations in breast-feeding infants of mothers receiving highly active antiretroviral therapy. Antimicrob. Agents Chemother. 53, 1170–1176 (2009).

    Article  Google Scholar 

  28. Milich, D. & Liang, T. J. Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. Hepatology 38, 1075–1086 (2003).

    Article  CAS  Google Scholar 

  29. Wang, Z. H. et al. Quantitative analysis of HBV DNA level and HBeAg titer in hepatitis B surface antigen positive mothers and their babies: HBeAg passage through the placenta and the rate of decay in babies. J. Med. Virol. 71, 360–366 (2003).

    Article  CAS  Google Scholar 

  30. Guo, Z. et al. Risk factors of HBV intrauterine transmission among HBsAg-positive pregnant women. J. Viral Hepatol. 20, 317–321 (2013).

    Article  CAS  Google Scholar 

  31. Yin, Y. et al. Identification of risk factors associated with immunoprophylaxis failure to prevent the vertical transmission of hepatitis B virus. J. Infect. 66, 447–452 (2013).

    Article  Google Scholar 

  32. Tse, K. et al. Immunoprophylaxis of babies borne to hepatitis B carrier mothers. Hong Kong Med. J. 12, 368–374 (2006).

    CAS  PubMed  Google Scholar 

  33. Burk, R. D. et al. Outcome of perinatal hepatitis B virus exposure is dependent on maternal virus load. J. Infect. Dis. 170, 1418–1423 (1994).

    Article  CAS  Google Scholar 

  34. Wiseman, E. et al. Perinatal transmission of hepatitis B virus: an Australian experience. MJA 109, 489–492 (2009).

    Google Scholar 

  35. Zou, H. et al. Virologic factors associated with failure to passive–active immunoprophylaxis in infants born to HBsAg-positive mothers. J. Viral Hepatol. 19, e18–e25 (2012).

    Article  CAS  Google Scholar 

  36. Yang, J. et al. Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus—a systematic review. Virol. J. 5, 100 (2008).

    Article  Google Scholar 

  37. Hu, Y. et al. Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus. BMC Pregnancy Childbirth 13, 119 (2013).

    Article  Google Scholar 

  38. Pan, C. Q. et al. Cesarean section reduces perinatal transmission of HBV Infection from hepatitis B surface antigen-positive women to their infants. Clin. Gastroenterol. Hepatol. http://dx.doi.org/10.1016/j.cgh.2013.04.026.

  39. Centers for Disease Control and Prevention (CDC) Implementation of newborn hepatitis B vaccination—worldwide, 2006. MMWR Morb. Mortal. Wkly Rep. 46, 1249–1252 (2006).

  40. Tran, T. T. et al. Hepatitis B Research Network (HBRN): maternal knowledge of children's hepatitis B infection and vaccination status [abstract]. Hepatology 58 (Suppl.), 622A–623A (2013).

    Google Scholar 

  41. Singhal, A. et al. Chronic HBV with pregnancy: reactivation flare causing fulminant hepatic failure. Annals Hepatol. 10, 233–236 (2011).

    Article  Google Scholar 

  42. Shaheen, A. A. & Myers, R. P. The outcomes of pregnancy in patients with cirrhosis: a population-based study. Liver Int. 30, 275–283 (2010).

    Article  Google Scholar 

  43. Kim, H. Y. et al. Outcome after discontinuing antiviral agents during pregnancy in women infected with hepatitis B. J. Clin. Virol. 56, 299–305 (2013).

    Article  CAS  Google Scholar 

  44. Nguyen, G. et al. Clinical course of hepatitis B virus infection during pregnancy. Aliment. Pharmacol. Ther. 29, 755–764 (2009).

    Article  CAS  Google Scholar 

  45. Han, L. et al. A meta-analysis of lamivudine for interruption of mother-to-child transmission of hepatitis B virus. World J. Gastroenterol. 17, 4321–4333 (2011).

    Article  CAS  Google Scholar 

  46. Xu, W. M. et al. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J. Viral Hepat. 16, 94–103 (2009).

    Article  Google Scholar 

  47. Yi, W., Liu, M., Chen, A. & Pan, C. The efficacy of lamivudine use in the second vs. third trimester of pregnancy in preventing vertical transmission of HBV in highly viremic mothers [abstract]. Hepatology 58 (Suppl.) 614A (2013).

    Google Scholar 

  48. Han, G.-R. et al. A prospective and open label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection. J. Hepatol. 55, 1215–1221 (2011).

    Article  CAS  Google Scholar 

  49. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International. Interim Report for 1 January through 31 January 2013. Wilmington, NC: Registry Coordinating Center; 2013 [online], (2012).

  50. Pan, C. Q. et al. Telbivudine prevents vertical transmission from HBeAg-positive women with chronic hepatitis B. Clin. Gastroenterol. Hepatol. 10, 520–526 (2012).

    Article  CAS  Google Scholar 

  51. Liu, M., Cai, H. & Yi, W. Safety of telbivudine treatment for chronic hepatitis B for the entire pregnancy. J. Viral Hepatol. 20 (Suppl. 1), 65–70 (2013).

    Article  Google Scholar 

  52. Han, G. R. et al. Long-term safety and efficacy of infants born to telbivudine-treated highly viremic mothers with HBeAg positive chronic hepatitis B (CHB) during 2nd or 3rd trimester [abstract]. Hepatology 58 (Suppl.), 654A (2013).

    Google Scholar 

  53. Pan, C. Q. et al. Tenofovir disoproxil fumarate for prevention of vertical transmission of hepatitis B virus infection by highly viremic pregnant women: a case series. Dig. Dis. Sci. 57, 2423–2429 (2012).

    Article  CAS  Google Scholar 

  54. Pan, C., Liu, M., Cai, H. & Yo, W. Safety of tenofovir disoproxil fumarate (TDF) treatment for the entire pregnancy in mothers with active chronic hepatitis B or cirrhosis [abstract]. Hepatology 58 (Suppl.), 624A (2013).

    Google Scholar 

  55. Greenup, A. J. et al. Efficacy and safety of tenofovir in pregnancy to prevent mother to baby transmission of HBV [abstract]. Hepatology 58 (Suppl.), 625A (2013).

    Google Scholar 

  56. EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection. European Association for the Study of the Liver. J. Hepatol. 57, 167–185 (2012).

  57. Connell, L. E. et al. Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes. Liver Int. 31, 1163–1170 (2011).

    Article  Google Scholar 

  58. Tse, K. Y. et al. The impact of maternal HBsAg carrier status on pregnancy outcomes: A case–control study. J. Hepatol. 43, 771–775 (2005).

    Article  CAS  Google Scholar 

  59. Lao, T. T. et al. Maternal hepatitis B surface antigen and incidence of pre-eclampsia. J. Viral Hepat. 20, 343–349 (2013).

    Article  CAS  Google Scholar 

  60. Bzowej, N. H. et al. ALT flares are infrequent during the course of pregnancy: perspectives from the Hepatitis B Research Network (HBRN) adult cohort study [abstract]. Hepatology 58 (Suppl.), 646A–647A (2013).

    Google Scholar 

  61. Giles, M. et al. Clinical and virological factors that predict post partum flares in pregnant women with chronic, HBV [abstract]. Hepatology 58 (Suppl.), 638A (2013).

    Google Scholar 

  62. Nguyen, V. et al. Prolonging antiviral therapy after pregnancy for prevention of perinatal HBV transmission does not abrogate post-partum flares [abstract]. Hepatology 58 (Suppl.), 641A (2013).

    Google Scholar 

  63. US Department of Health & Human Services. FDA Viral hepatitis therapies [online], (2013).

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Author information

Authors and Affiliations

  1. UC San Diego Health System, 200 West Arbor Drive, San Diego, 92103, CA, USA

    Heather Patton

  2. Cedars Sinai Medical Center, 8635 West 3rd Street, Suite 590W, Los Angeles, 90048, CA, USA

    Tram T. Tran

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  1. Heather Patton
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The authors contributed equally to all aspects in the production of this article.

Corresponding author

Correspondence to Tram T. Tran.

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Competing interests

T.T.T. acts as a consultant, advisor and/or speaker for Bristol–Myers–Squibb, Gilead Sciences and Novartis. H.P. declares no competing interests.

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Patton, H., Tran, T. Management of hepatitis B during pregnancy. Nat Rev Gastroenterol Hepatol 11, 402–409 (2014). https://doi.org/10.1038/nrgastro.2014.30

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