Abstract
Purpose
Chronic hepatitis B virus (HBV) infection remains endemic and continues to cause significant morbidity and mortality. It is a global health issue and the World Health Organization aims to eradicate HBV by 2030. Since vertical transmission accounts for the majority of chronic HBV infection, pregnancy offers an excellent opportunity to achieve complete HBV eradication by providing effective immunization of the offspring.
Methods
We reviewed recent publications identified from PubMed database using a combination of the relevant keywords for HBV, pregnancy, vertical transmission, immunoprophylaxis failure and antiviral treatment.
Results
We summarized the evidence of factors associated with, and measures to reduce and prevent maternal to child transmission, including the use of antiviral treatment during pregnancy to prevent immunoprophylaxis failure. Evidence suggested that highly viremia mother can be offered antenatal antiviral treatment to prevent immunoprophylaxis failure. We elaborated the viral load threshold to start maternal antiviral treatment and the importance of timely neonatal vaccination. A clinical algorithm to manage HBV carriers during pregnancy was proposed.
Conclusion
Eradication of HBV is achievable with optimal management of HBV carriers, especially during pregnancy by interruption of vertical transmission. Routine antenatal screening and neonatal immunoprophylaxis remain the key measures to reduce the global HBV burden, and additional antenatal antiviral treatment could further minimize the chance of persistent infection in newborns.
Similar content being viewed by others
References
World Health Organization. Global Hepatitis Report (2017). https://apps.who.int/iris/bitstream/handle/10665/255016/9789241565455-eng;jsessionid=B32461CA5A37D9C9D7A90BCE32C43F92?sequence=1. Accessed 1 Sep 2018
Stanaway JD, Flaxman AD, Naghavi M et al (2016) The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet 388(10049):1081–1088. https://doi.org/10.1016/S0140-6736(16)30579-7 (PubMed PMID: 27394647; PubMed Central PMCID: PMCPMC5100695)
World Health Organization. Hepatitis B (2018). https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-b. Accessed 1 Sep 2018
World Health Organization. Global Health Sector Strategy on viral hepatitis 2016–2021, towards ending viral hepatitis (2016). https://apps.who.int/iris/bitstream/handle/10665/246177/WHO-HIV-2016.06-eng.pdf?sequence=1. Accessed 1 Sep 2018
Edmunds WJ, Medley GF, Nokes DJ et al (1993) The influence of age on the development of the hepatitis B carrier state. Proc Biol Sci 253(1337):197–201. https://doi.org/10.1098/rspb.1993.0102 (PubMed PMID: 8397416)
Lao TT, Sahota DS, Chan PKS (2018) Three decades of neonatal vaccination has greatly reduced antenatal prevalence of hepatitis B virus infection among gravidae covered by the program. J Infect 76(6):543–549. https://doi.org/10.1016/j.jinf.2018.04.003 (PubMed PMID: 29742467)
Centers for Disease Control and Prevention. Viral Hepatitis. Hepatitis B information. Perinatal Transmission. https://www.cdc.gov/hepatitis/hbv/perinatalxmtn.htm. Accessed 1 Sep 2018
Thimme R, Wieland S, Steiger C et al (2003) CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol 77(1):68–76 (PubMed PMID: 12477811; PubMed Central PMCID: PMCPMC140637)
Milich DR, Jones JE, Hughes JL et al (1990) Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proc Natl Acad Sci USA 87(17):6599–6603 (PubMed PMID: 2395863; PubMed Central PMCID: PMCPMC54584)
Trehanpati N, Hissar S, Shrivastav S et al (2013) Immunological mechanisms of hepatitis B virus persistence in newborns. Indian J Med Res 138(5):700–710 (PubMed PMID: 24434322; PubMed Central PMCID: PMCPMC3928700)
Shrivastava S, TrehanPati N, Patra S et al (2013) Increased regulatory T cells and impaired functions of circulating CD8 T lymphocytes is associated with viral persistence in Hepatitis B virus-positive newborns. J Viral Hepat 20(8):582–591. https://doi.org/10.1111/jvh.12078 (PubMed PMID: 23808997)
Lao TT, Leung TY, Chan HL et al (2015) Effect of pregnancy on the activity and infectivity of hepatitis B virus in women with chronic hepatitis B infection. Hong Kong Med J 21(Suppl 7):S4–7 (PubMed PMID: 26908264)
Soderstrom A, Norkrans G, Lindh M (2003) Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission. Scand J Infect Dis 35(11–12):814–819 (PubMed PMID: 14723355)
Kushner T, Shaw PA, Kalra A et al (2018) Incidence, determinants and outcomes of pregnancy-associated hepatitis B flares: a regional hospital-based cohort study. Liver Int 38(5):813–820. https://doi.org/10.1111/liv.13594 (PubMed PMID: 28941137)
Chang CY, Aziz N, Poongkunran M et al (2016) Serum alanine aminotransferase and hepatitis B DNA flares in pregnant and postpartum women with chronic hepatitis B. Am J Gastroenterol 111(10):1410–1415. https://doi.org/10.1038/ajg.2016.296 (PubMed PMID: 27456990)
Liu J, Bi Y, Xu C et al (2015) Kinetic changes of viremia and viral antigens of hepatitis B virus during and after pregnancy. Medicine (Baltimore) 94(45):e2001. https://doi.org/10.1097/MD.0000000000002001 (PubMed PMID: 26559291; PubMed Central PMCID: PMCPMC4912285)
Giles M, Visvanathan K, Lewin S et al (2015) Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Gut 64(11):1810–1815. https://doi.org/10.1136/gutjnl-2014-308211 (PubMed PMID: 25431458)
Liu J, Wang J, Qi C et al (2017) Baseline hepatitis B virus titer predicts initial postpartum hepatic flare: a multicenter prospective study. J Clin Gastroenterol. https://doi.org/10.1097/MCG.0000000000000877 (PubMed PMID: 28654554)
Yi W, Pan CQ, Li MH et al (2018) The characteristics and predictors of postpartum hepatitis flares in women with chronic hepatitis B. Am J Gastroenterol 113(5):686–693. https://doi.org/10.1038/s41395-018-0010-2 (PubMed PMID: 29487412)
Wong HY, Tan JY, Lim CC (2004) Abnormal liver function tests in the symptomatic pregnant patient: the local experience in Singapore. Ann Acad Med Singapore 33(2):204–208 (PubMed PMID: 15098635)
Tan HH, Lui HF, Chow WC (2008) Chronic hepatitis B virus (HBV) infection in pregnancy. Hepatol Int 2(3):370–375. https://doi.org/10.1007/s12072-008-9063-4 (PubMed PMID: 19669267; PubMed Central PMCID: PMCPMC2716894)
Lin HH, Wu WY, Kao JH et al (2006) Hepatitis B post-partum e antigen clearance in hepatitis B carrier mothers: correlation with viral characteristics. J Gastroenterol Hepatol 21(3):605–609. https://doi.org/10.1111/j.1440-1746.2006.04198.x (PubMed PMID: 16638107)
Wong VC, Lee AK, Ip HM (1980) Transmission of hepatitis B antigens from symptom free carrier mothers to the fetus and the infant. Br J Obstet Gynaecol 87(11):958–965 (PubMed PMID: 7437368)
Beasley RP, Trepo C, Stevens CE et al (1977) The e antigen and vertical transmission of hepatitis B surface antigen. Am J Epidemiol 105(2):94–98 (PubMed PMID: 835566)
Chen SC, Toy M, Yeh JM et al (2013) Cost-effectiveness of augmenting universal hepatitis B vaccination with immunoglobin treatment. Pediatrics 131(4):e1135–e1143. https://doi.org/10.1542/peds.2012-1262 (PubMed PMID: 23530168; PubMed Central PMCID: PMCPMC4015450)
Isaacs D, Kilham HA, Alexander S et al (2011) Ethical issues in preventing mother-to-child transmission of hepatitis B by immunisation. Vaccine 29(37):6159–6162. https://doi.org/10.1016/j.vaccine.2011.06.065 (PubMed PMID: 21723352)
Lao TT, Cheung KL, Wong V (2015) Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women. Vaccine 33(1):15–16. https://doi.org/10.1016/j.vaccine.2014.05.036 (PubMed PMID: 25017181)
Wiseman E, Fraser MA, Holden S et al (2009) Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust 190(9):489–492 (PubMed PMID: 19413519)
Zou H, Chen Y, Duan Z et al (2012) Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 19(2):e18–25. https://doi.org/10.1111/j.1365-2893.2011.01492.x (PubMed PMID: 22239517)
Wen WH, Chang MH, Zhao LL et al (2013) Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol. 59(1):24–30. https://doi.org/10.1016/j.jhep.2013.02.015 (PubMed PMID: 23485519)
Zhang L, Gui X, Wang B et al (2014) A study of immunoprophylaxis failure and risk factors of hepatitis B virus mother-to-infant transmission. Eur J Pediatr 173(9):1161–1168. https://doi.org/10.1007/s00431-014-2305-7 (PubMed PMID: 24699981)
Liu CP, Zeng YL, Zhou M et al (2015) Factors associated with mother-to-child transmission of hepatitis B virus despite immunoprophylaxis. Intern Med 54(7):711–716. https://doi.org/10.2169/internalmedicine.54.3514 (PubMed PMID: 25832930)
Schillie S, Walker T, Veselsky S et al (2015) Outcomes of infants born to women infected with hepatitis B. Pediatrics 135(5):e1141–e1147. https://doi.org/10.1542/peds.2014-3213 (PubMed PMID: 25896839)
Cheung KW, Seto MTY, Kan ASY et al (2018) Immunoprophylaxis failure of infants born to hepatitis B carrier mothers following routine vaccination. Clin Gastroenterol Hepatol 16(1):144–145. https://doi.org/10.1016/j.cgh.2017.07.013 (PubMed PMID: 28733258)
Wang C, Wang C, Jia ZF et al (2016) Protective effect of an improved immunization practice of mother-to-infant transmission of hepatitis B virus and risk factors associated with immunoprophylaxis failure. Medicine (Baltimore) 95(34):e4390. https://doi.org/10.1097/MD.0000000000004390 (PubMed PMID: 27559947; PubMed Central PMCID: PMCPMC5400313)
Kang W, Ding Z, Shen L et al (2014) 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 32(27):3362–3366. https://doi.org/10.1016/j.vaccine.2014.04.045 (PubMed PMID: 24793939)
Ji Z, Wang T, Shao Z et al (2014) A population-based study examining hepatitis B virus infection and immunization rates in Northwest China. PLoS One 9(5):e97474. https://doi.org/10.1371/journal.pone.0097474 (PubMed PMID: 24832483; PubMed Central PMCID: PMCPMC4022626)
Cheung KW, Seto MT, Wong SF (2013) Towards complete eradication of hepatitis B infection from perinatal transmission: review of the mechanisms of in utero infection and the use of antiviral treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol 169(1):17–23. https://doi.org/10.1016/j.ejogrb.2013.02.001 (PubMed PMID: 23465469)
Yang M, Qin Q, Fang Q et al (2017) Cesarean section to prevent mother-to-child transmission of hepatitis B virus in China: a meta-analysis. BMC Pregnancy Childbirth 17(1):303. https://doi.org/10.1186/s12884-017-1487-1 (PubMed PMID: 28899348; PubMed Central PMCID: PMCPMC5596961)
Cheung KW, Seto MTY, So PL et al (2019) The effect of rupture of membranes and labour on the risk of hepatitis B vertical transmission: prospective multicentre observational study. Eur J Obstet Gynecol Reprod Biol 232:97–100. https://doi.org/10.1016/j.ejogrb.2018.11.017 (PubMed PMID: 30504033)
Eke AC, Eleje GU, Eke UA, et al. (2017) Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus. Cochrane Database Syst Rev 11;2:CD008545. https://doi.org/10.1002/14651858.CD008545.pub2 (PubMed PMID: 28188612)
Jourdain G, Ngo-Giang-Huong N, Harrison L et al (2018) Tenofovir versus placebo to prevent perinatal transmission of hepatitis B. N Engl J Med. 378(10):911–923. https://doi.org/10.1056/NEJMoa1708131 (PubMed PMID: 29514030; PubMed Central PMCID: PMCPMC5895092)
Shouval D (2003) Hepatitis B vaccines. J Hepatol 39(Suppl 1):S70–S76 (PubMed PMID: 14708681)
European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L (2017) EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370–398. doi: 10.1016/j.jhep.2017.03.021. (PubMed PMID: 28427875)
Sarin SK, Kumar M, Lau GK et al. (2016) Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update Hepatol Int 10(1):1–98. 10.1007/s12072-015-9675-4https://doi.org/10.1007/s12072-015-9675-4 (PubMed PMID: 26563120; PubMed Central PMCID: PMCPMC4722087)
Terrault NA, Lok ASF, McMahon BJ et al (2018) Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 67(4):1560–1599. https://doi.org/10.1002/hep.29800 (PubMed PMID: 29405329)
Yi W, Pan CQ, Hao J et al (2014) Risk of vertical transmission of hepatitis B after amniocentesis in HBs antigen-positive mothers. J Hepatol 60(3):523–529. https://doi.org/10.1016/j.jhep.2013.11.008 (PubMed PMID: 24269471)
Dusheiko G (2018) A shift in thinking to reduce mother-to-infant transmission of hepatitis B. N Engl J Med 378(10):952–953. https://doi.org/10.1056/NEJMe1801662 (PubMed PMID: 29514035)
Mandelbrot L, Landreau-Mascaro A, Rekacewicz C et al (2001) Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA 285(16):2083–2093 (PubMed PMID: 11311097)
Gupta R, Warren T, Wald A (2007) Genital herpes. Lancet 370(9605):2127–2137. https://doi.org/10.1016/S0140-6736(07)61908-4 (PubMed PMID: 18156035)
Brown RS Jr, McMahon BJ, Lok AS et al (2016) Antiviral therapy in chronic hepatitis B viral infection during pregnancy: a systematic review and meta-analysis. Hepatology 63(1):319–333. https://doi.org/10.1002/hep.28302 (PubMed PMID: 26565396)
Brown RS Jr, Verna EC, Pereira MR et al (2012) Hepatitis B virus and human immunodeficiency virus drugs in pregnancy: findings from the Antiretroviral Pregnancy Registry. J Hepatol 57(5):953–959. https://doi.org/10.1016/j.jhep.2012.06.031 (PubMed PMID: 22766470)
Hyun MH, Lee YS, Kim JH et al (2017) Systematic review with meta-analysis: the efficacy and safety of tenofovir to prevent mother-to-child transmission of hepatitis B virus. Aliment Pharmacol Ther 45(12):1493–1505. https://doi.org/10.1111/apt.14068 (PubMed PMID: 28436552)
Hu YH, Liu M, Yi W et al (2015) Tenofovir rescue therapy in pregnant females with chronic hepatitis B. World J Gastroenterol 21(8):2504–2509. https://doi.org/10.3748/wjg.v21.i8.2504 (PubMed PMID: 25741161; PubMed Central PMCID: PMCPMC4342930)
Pan CQ, Duan Z, Dai E et al (2016) Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med 374(24):2324–2334. https://doi.org/10.1056/NEJMoa1508660 (PubMed PMID: 27305192)
Schillie S, Murphy TV, Fenlon N et al (2015) Update: shortened interval for postvaccination serologic testing of infants born to hepatitis B-infected mothers. MMWR Morb Mortal Wkly Rep 64(39):1118–1120. https://doi.org/10.15585/mmwr.mm6439a6 (PubMed PMID: 26447601)
Cheung KW, Seto MTY, Ng EHY (2018) Tenofovir to prevent perinatal transmission of hepatitis B. N Engl J Med 378(24):2349–2350. https://doi.org/10.1056/NEJMc1805396 (PubMed PMID: 29900727)
Grigsby IF, Pham L, Mansky LM, et al. (2010) Tenofovir-associated bone density loss. Ther Clin Risk Manag 6:41–7. (PubMed PMID: 20169035; PubMed Central PMCID: PMCPMC2817787)
Mir S, Jao J, Brittain K, et al. (2017) Tenofovir exposure in utero and linear growth in HIV-exposed, uninfected infants. AIDS 31(1):97–104. https://doi.org/10.1097/QAD.0000000000001302 (PubMed PMID: 27898591; PubMed Central PMCID: PMCPMC5814299)
Jao J, Abrams EJ, Phillips T et al (2016) In utero tenofovir exposure is not associated with fetal long bone growth. Clin Infect Dis 62(12):1604–1609. https://doi.org/10.1093/cid/ciw159 (PubMed PMID: 27009251; PubMed Central PMCID: PMCPMC4885649)
Hall AM, Hendry BM, Nitsch D et al (2011) Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis 57(5):773–780. https://doi.org/10.1053/j.ajkd.2011.01.022 (PubMed PMID: 21435764)
Wait S, Kell E, Hamid S et al (2016) Hepatitis B and hepatitis C in southeast and southern Asia: challenges for governments. Lancet Gastroenterol Hepatol 1(3):248–255. https://doi.org/10.1016/S2468-1253(16)30031-0 (PubMed PMID: 28404097)
Liu M, Cai H, Yi W (2013) Safety of telbivudine treatment for chronic hepatitis B for the entire pregnancy. J Viral Hepat 20(Suppl 1):65–70. https://doi.org/10.1111/jvh.12066 (PubMed PMID: 23458527)
Shang J, Wen Q, Wang CC et al (2017) Safety and efficacy of telbivudine for chronic hepatitis B during the entire pregnancy: Long-term follow-up. J Viral Hepat 24(Suppl 1):43–48. https://doi.org/10.1111/jvh.12785 (PubMed PMID: 29082646)
Sun W, Zhao S, Ma L et al (2017) Telbivudine treatment started in early and middle pregnancy completely blocks HBV vertical transmission. BMC Gastroenterol 17(1):51. https://doi.org/10.1186/s12876-017-0608-7 (PubMed PMID: 28407735; PubMed Central PMCID: PMCPMC5390436)
Pan CQ, Yi W, Liu M et al (2017) Lamivudine therapy during the second vs the third trimester for preventing transmission of chronic hepatitis B. J Viral Hepat 24(3):246–252. https://doi.org/10.1111/jvh.12640 (PubMed PMID: 28025872)
Hu Y, Xu C, Xu B et al (2018) Safety and efficacy of telbivudine in late pregnancy to prevent mother-to-child transmission of hepatitis B virus: A multicenter prospective cohort study. J Viral Hepat 25(4):429–437. https://doi.org/10.1111/jvh.12834 (PubMed PMID: 29193547)
Author information
Authors and Affiliations
Contributions
KWC, MTYS and TTHL: project development, manuscript writing.
Corresponding author
Ethics declarations
Conflict of interest
All authors have no conflicts of interest to declare.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Cheung, K.W., Seto, M.T.Y. & Lao, T.TH. Prevention of perinatal hepatitis B virus transmission. Arch Gynecol Obstet 300, 251–259 (2019). https://doi.org/10.1007/s00404-019-05190-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00404-019-05190-0