Current recommendations of managing HBV infection in preconception or pregnancy
James S. Park, Calvin Pan
Current recommendations of managing HBV infection in preconception or pregnancy
Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation worldwide. Management of chronic hepatitis B during pregnancy is challenging. Transmission of hepatitis B to infants still occurs perinatally although immunoprophylaxis is widely available for infants born to mothers with chronic hepatitis B infection. The emerging data suggest that initiation of antiviral therapy in the beginning of the third trimester in highly viremic mothers can prevent immunoprophylaxis failure in their infants. The available drug safety data show that lamivudine, telbivudine and tenofovir are generally safe to be used during the pregnancy. In order to minimize the fetal exposure to the antiviral medication, antiviral therapy during the pregnancy should be limited to a selected group of patients with cirrhosis, high hepatitis B viral load, or prior history immunoprophylaxis failure. An elective Caesarean section may reduce the risk of perinatal transmission. For those females planning for pregnancy or in early stage of pregnancy, communication and follow-up among obstetrician, gastroenterologist, and primary care physician are important. In this article, we will review the features of hepatitis B infection before, during and after the pregnancy; the risk factors that increase mother-to-child transmission; safety data on antiviral drug use during pregnancy; and the potential role of Caesarean section in selected cases.
antiviral therapy / Caesarean section / cirrhosis / hepatitis B / immunoprophylaxis / mother-to-child transmission / pregnancy / prevention
[1] |
World Health Organization. Hepatitis B Fact sheet, July 2012.
|
[2] |
Gambarin-Gelwan M. Hepatitis B in pregnancy. Clin Liver Dis 2007; 11(4): 945–963
CrossRef
Pubmed
Google scholar
|
[3] |
Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW; Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008; 57(RR-8): 1–20
Pubmed
|
[4] |
Lok ASF, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50(3): 661–662
CrossRef
Pubmed
Google scholar
|
[5] |
Tong MJ, Pan CQ, Hann HW, Kowdley KV, Han SH, Min AD, Leduc TS. The management of chronic hepatitis B in Asian Americans. Dig Dis Sci 2011; 56(11): 3143–3162
CrossRef
Pubmed
Google scholar
|
[6] |
Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol 2008; 6(12): 1315–1341, quiz 1286
CrossRef
Pubmed
Google scholar
|
[7] |
Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, Tong MJ. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol 2012; 10(5): 452–459
CrossRef
Pubmed
Google scholar
|
[8] |
Law ST, Li KK, Ho YY. Nephrotoxicity, including acquired Fanconi’s syndrome, caused by adefovir dipivoxil — is there a safe dose? J Clin Pharm Ther 2012; 37(2): 128–131
CrossRef
Pubmed
Google scholar
|
[9] |
Wang M, Da Y, Cai H, Lu Y, Wu L, Jia J. Telbivudine myopathy in a patient with chronic hepatitis B. Int J Clin Pharmacol 2012; 34(3): 422–425
CrossRef
Pubmed
Google scholar
|
[10] |
Tse KY, Ho LF, Lao T. The impact of maternal HBsAg carrier status on pregnancy outcomes: a case-control study. J Hepatol 2005; 43(5): 771–775
CrossRef
Pubmed
Google scholar
|
[11] |
Reddick KL, Jhaveri R, Gandhi M, James AH, Swamy GK. Pregnancy outcomes associated with viral hepatitis. J Viral Hepat 2011; 18(7): e394–e398
CrossRef
Pubmed
Google scholar
|
[12] |
Safir A, Levy A, Sikuler E, Sheiner E. Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome. Liver Int 2010; 30(5): 765–770
CrossRef
Pubmed
Google scholar
|
[13] |
Wong S, Chan LY, Yu V, Ho L. Hepatitis B carrier and perinatal outcome in singleton pregnancy. Am J Perinatol 1999; 16(9): 485–488
CrossRef
Pubmed
Google scholar
|
[14] |
Terazawa S, Kojima M, Yamanaka T, Yotsumoto S, Okamoto H, Tsuda F, Miyakawa Y, Mayumi M. Hepatitis B virus mutants with precore-region defects in two babies with fulminant hepatitis and their mothers positive for antibody to hepatitis B e antigen. Pediatr Res 1991; 29(1): 5–9
CrossRef
Pubmed
Google scholar
|
[15] |
Mattsson R, Mattsson A, Holmdahl R, Whyte A, Rook GA. Maintained pregnancy levels of oestrogen afford complete protection from post-partum exacerbation of collagen-induced arthritis. Clin Exp Immunol 1991; 85(1): 41–47
CrossRef
Pubmed
Google scholar
|
[16] |
Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol 2003; 38(1): 13–22
CrossRef
Pubmed
Google scholar
|
[17] |
Tan HH, Lui HF, Chow WC. Chronic hepatitis B virus (HBV) infection in pregnancy. Hepatol Int 2008; 2(3): 370–375
CrossRef
Pubmed
Google scholar
|
[18] |
Söderström A, Norkrans G, Lindh M. Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission. Scand J Infect Dis 2003; 35(11–12): 814–819
CrossRef
Pubmed
Google scholar
|
[19] |
Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. FASEB J 2005; 19(7): 681–693
CrossRef
Pubmed
Google scholar
|
[20] |
Giles ML, Visvanathan K, Lewin SR, Sasadeusz J. Chronic hepatitis B infection and pregnancy. Obstet Gynecol Surv 2012; 67(1): 37–44
CrossRef
Pubmed
Google scholar
|
[21] |
Tran T.Hepatitis B: treatment to prevent perinatal transmission. Clinical Obs Gyn 2012;55(2): 541–549
|
[22] |
Nie R, Jin L, Zhang H, Xu B, Chen W, Zhu G. Presence of hepatitis B virus in oocytes and embryos: a risk of hepatitis B virus transmission during in vitro fertilization. Fertil Steril 2011; 95(5): 1667–1671
CrossRef
Pubmed
Google scholar
|
[23] |
Pan CQ, Lee HM. Antiviral therapy for chronic hepatitis B in pregnancy. Semin Liver Dis 2013; 33(2): 138–146
CrossRef
Pubmed
Google scholar
|
[24] |
Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, Tong MJ. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol 2012; 10(5): 452–459
CrossRef
Pubmed
Google scholar
|
[25] |
Antiviral Pregnancy Registry (APR).. Antiviral Pregnancy Registry Interim Report 1, January 1989 through 31 January 2012. Available at:
|
[26] |
Alter MJ. Epidemiology of hepatitis B in Europe and worldwide. J Hepatol 2003; 39(Suppl 1): S64–S69
CrossRef
Pubmed
Google scholar
|
[27] |
Xu WM, Cui YT, Wang L, Yang H, Liang ZQ, Li XM, Zhang SL, Qiao FY, Campbell F, Chang CN, Gardner S, Atkins M. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepat 2009; 16(2): 94–103
CrossRef
Pubmed
Google scholar
|
[28] |
Xu DZ, Yan YP, Choi BC, Xu JQ, Men K, Zhang JX, Liu ZH, Wang FS. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol 2002; 67(1): 20–26
CrossRef
Pubmed
Google scholar
|
[29] |
Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012; 19(2): e18–e25
CrossRef
Pubmed
Google scholar
|
[30] |
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(9): 489–492
Pubmed
|
[31] |
Yi W, Pan CQ, Hao J, Hu Y, Liu M, Li L, Liang D. Risk of vertical transmission of hepatitis B after amniocentesis in HBs antigen-positive mothers. J Hepatol 2014; 60(3): 523–529
CrossRef
Pubmed
Google scholar
|
[32] |
Han GR, Cao MK, Zhao W, Jiang HX, Wang CM, Bai SF, Yue X, Wang GJ, Tang X, Fang ZX. 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 2011; 55(6): 1215–1221
CrossRef
Pubmed
Google scholar
|
[33] |
Zhang H, Pan CQ, Pang Q, Tian R, Yan M, Liu X. Telbivudine or lamivudine use in late pregnancy safely reduce perinatal transmission of hepatitis B virus in real-life practice. Hepatology 2014; [Accepted Article ]
CrossRef
Google scholar
|
[34] |
Pan CQ, Zou HB, Chen Y, Zhang X, Zhang H, Li J, Duan Z. Caesarean section reduces perinatal transmission of hepatitis B virus infection from hepatitis B surface antigen-positive women to their infants. Clin Gastroenterol Hepatol 2013; 11(10): 1349–1355
CrossRef
Pubmed
Google scholar
|
[35] |
Han ZH, Zhong LH, Wang J, Zhao QL, Sun YG, Li LW, Cao LH, Hao XC, Zhuang H. The impact of antepartum injection of hepatitis B immunoglobulin on maternal serum HBV DNA and anti-HBs in the newborns. Chin J Intern Med (Zhonghua Nei Ke Za Zhi) 2007; 46(5): 376–378 (in Chinese)
Pubmed
|
[36] |
Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis. BMJ 2006; 332(7537): 328–336
CrossRef
Pubmed
Google scholar
|
[37] |
Wong VC, Lee AK, Ip HM. Transmission of hepatitis B antigens from symptom free carrier mothers to the fetus and the infant. Br J Obstet Gynaecol 1980; 87(11): 958–965
CrossRef
Pubmed
Google scholar
|
[38] |
Beasley RP, Stevens CE, Shiao IS, Meng HC. Evidence against breast-feeding as a mechanism for vertical transmission of hepatitis B. Lancet 1975; 306 (7938): 740–741
CrossRef
Pubmed
Google scholar
|
[39] |
Hill JB, Sheffield JS, Kim MJ, Alexander JM, Sercely B, Wendel GD. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet Gynecol 2002; 99(6): 1049–1052
CrossRef
Pubmed
Google scholar
|
[40] |
Van Rompay KK, Hamilton M, Kearney B, Bischofberger N. Pharmacokinetics of tenofovir in breast milk of lactating rhesus macaques. Antimicrob Agents Chemother 2005; 49(5): 2093–2094
CrossRef
Pubmed
Google scholar
|
[41] |
Zhang L, Gui X, Fan J, Wang B, Ji H, Yisilafu R, Li F, Zhou Y, Tong Y, Kong X, Ye P, Zong L. Breast feeding and immunoprophylaxis efficacy of mother-to-child transmission of hepatitis B virus. J Matern Fetal Neonatal Med 2014; 27(2): 182–186
CrossRef
Pubmed
Google scholar
|
/
〈 | 〉 |