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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

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Front. Med.    2014, Vol. 8 Issue (2) : 158-165    https://doi.org/10.1007/s11684-014-0340-4
REVIEW
Current recommendations of managing HBV infection in preconception or pregnancy
James S. Park, Calvin Pan()
Division of Gastroenterology, Department of Medicine, NYU Langone Medical Center, NYU School of Medicine, New York 10016, USA
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Abstract

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.
Keywords antiviral therapy      Caesarean section      cirrhosis      hepatitis B      immunoprophylaxis      mother-to-child transmission      pregnancy      prevention     
Corresponding Author(s): Calvin Pan   
Issue Date: 21 May 2014
 Cite this article:   
James S. Park,Calvin Pan. Current recommendations of managing HBV infection in preconception or pregnancy[J]. Front. Med., 2014, 8(2): 158-165.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-014-0340-4
https://academic.hep.com.cn/fmd/EN/Y2014/V8/I2/158
Fig.1  Active CHB during pregnancy.
Fig.2  Non-active CHB during pregnancy.
Category FDA description ?Anti-HBV drug
A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is ?no evidence of risk in later trimesters)
B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in ?pregnant women or animal studies, which have shown an adverse effect, but adequate and well-controlled studies in pregnant ?women have failed to demonstrate a risk to the fetus in any trimester ?Telbivudine
?Tenofovir
C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in ?humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks ?Lamivudine
?Entecavir
?Adefovir
?Interferon
D There is positive evidence of human fetal risk based on adverse-reaction data from investigational or marketing experience or ?studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
X Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on ?adverse-reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant ?women clearly outweigh potential benefits
Tab.1  FDA pregnancy risk categories for anti-HBV drug
1 World Health Organization. Hepatitis B Fact sheet, July 2012.
2 M Gambarin-Gelwan. Hepatitis B in pregnancy. Clin Liver Dis 2007; 11(4): 945–963
https://doi.org/10.1016/j.cld.2007.08.004 pmid: 17981236
3 CM Weinbaum, I Williams, EE Mast, SA Wang, L Finelli, A Wasley, SM Neitzel, JW Ward; 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
pmid: 18802412
4 ASF Lok, BJ McMahon. Chronic hepatitis B: update 2009. Hepatology 2009; 50(3): 661–662
https://doi.org/10.1002/hep.23190 pmid: 19714720
5 MJ Tong, CQ Pan, HW Hann, KV Kowdley, SH Han, AD Min, TS Leduc. The management of chronic hepatitis B in Asian Americans. Dig Dis Sci 2011; 56(11): 3143–3162
https://doi.org/10.1007/s10620-011-1841-5 pmid: 21935699
6 EB Keeffe, DT Dieterich, SH Han, IM Jacobson, P Martin, ER Schiff, H Tobias. 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
https://doi.org/10.1016/j.cgh.2008.08.021 pmid: 18845489
7 CQ Pan, ZP Duan, KR Bhamidimarri, HB Zou, XF Liang, J Li, MJ Tong. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol 2012; 10(5): 452–459
https://doi.org/10.1016/j.cgh.2011.10.041 pmid: 22079509
8 ST Law, KK Li, YY Ho. Nephrotoxicity, including acquired Fanconi’s syndrome, caused by adefovir dipivoxil — is there a safe dose? J Clin Pharm Ther 2012; 37(2): 128–131
https://doi.org/10.1111/j.1365-2710.2011.01278.x pmid: 21714795
9 M Wang, Y Da, H Cai, Y Lu, L Wu, J Jia. Telbivudine myopathy in a patient with chronic hepatitis B. Int J Clin Pharmacol 2012; 34(3): 422–425
https://doi.org/10.1007/s11096-012-9633-3 pmid: 22527478
10 KY Tse, LF Ho, T Lao. The impact of maternal HBsAg carrier status on pregnancy outcomes: a case-control study. J Hepatol 2005; 43(5): 771–775
https://doi.org/10.1016/j.jhep.2005.05.023 pmid: 16139923
11 KL Reddick, R Jhaveri, M Gandhi, AH James, GK Swamy. Pregnancy outcomes associated with viral hepatitis. J Viral Hepat 2011; 18(7): e394–e398
https://doi.org/10.1111/j.1365-2893.2011.01436.x pmid: 21692952
12 A Safir, A Levy, E Sikuler, E Sheiner. 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
https://doi.org/10.1111/j.1478-3231.2010.02218.x pmid: 20214739
13 S Wong, LY Chan, V Yu, L Ho. Hepatitis B carrier and perinatal outcome in singleton pregnancy. Am J Perinatol 1999; 16(9): 485–488
https://doi.org/10.1055/s-1999-6802 pmid: 10774765
14 S Terazawa, M Kojima, T Yamanaka, S Yotsumoto, H Okamoto, F Tsuda, Y Miyakawa, M Mayumi. 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
https://doi.org/10.1203/00006450-199101000-00002 pmid: 2000259
15 R Mattsson, A Mattsson, R Holmdahl, A Whyte, GA Rook. Maintained pregnancy levels of oestrogen afford complete protection from post-partum exacerbation of collagen-induced arthritis. Clin Exp Immunol 1991; 85(1): 41–47
https://doi.org/10.1111/j.1365-2249.1991.tb05679.x pmid: 2070561
16 KW Beagley, CM Gockel. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol 2003; 38(1): 13–22
https://doi.org/10.1016/S0928-8244(03)00202-5 pmid: 12900050
17 HH Tan, HF Lui, WC Chow. Chronic hepatitis B virus (HBV) infection in pregnancy. Hepatol Int 2008; 2(3): 370–375
https://doi.org/10.1007/s12072-008-9063-4 pmid: 19669267
18 A Söderström, G Norkrans, M Lindh. Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission. Scand J Infect Dis 2003; 35(11–12): 814–819
https://doi.org/10.1080/00365540310016547 pmid: 14723355
19 JS Hunt, MG Petroff, RH McIntire, C Ober. HLA-G and immune tolerance in pregnancy. FASEB J 2005; 19(7): 681–693
https://doi.org/10.1096/fj.04-2078rev pmid: 15857883
20 ML Giles, K Visvanathan, SR Lewin, J Sasadeusz. Chronic hepatitis B infection and pregnancy. Obstet Gynecol Surv 2012; 67(1): 37–44
https://doi.org/10.1097/OGX.0b013e31823e464b pmid: 22278077
21 T. TranHepatitis B: treatment to prevent perinatal transmission. Clinical Obs Gyn 2012;55(2): 541–549
22 R Nie, L Jin, H Zhang, B Xu, W Chen, G Zhu. 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
https://doi.org/10.1016/j.fertnstert.2010.12.043 pmid: 21269614
23 CQ Pan, HM Lee. Antiviral therapy for chronic hepatitis B in pregnancy. Semin Liver Dis 2013; 33(2): 138–146
https://doi.org/10.1055/s-0033-1345718 pmid: 23749670
24 CQ Pan, ZP Duan, KR Bhamidimarri, HB Zou, XF Liang, J Li, MJ Tong. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol 2012; 10(5): 452–459
https://doi.org/10.1016/j.cgh.2011.10.041 pmid: 22079509
25 Antiviral Pregnancy Registry (APR).. Antiviral Pregnancy Registry Interim Report 1, January 1989 through 31 January 2012. Available at: 2012. Accessed November 1, 2012
26 MJ Alter. Epidemiology of hepatitis B in Europe and worldwide. J Hepatol 2003; 39(Suppl 1): S64–S69
https://doi.org/10.1016/S0168-8278(03)00141-7 pmid: 14708680
27 WM Xu, YT Cui, L Wang, H Yang, ZQ Liang, XM Li, SL Zhang, FY Qiao, F Campbell, CN Chang, S Gardner, M Atkins. 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
https://doi.org/10.1111/j.1365-2893.2008.01056.x pmid: 19175878
28 DZ Xu, YP Yan, BC Choi, JQ Xu, K Men, JX Zhang, ZH Liu, FS Wang. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol 2002; 67(1): 20–26
https://doi.org/10.1002/jmv.2187 pmid: 11920813
29 H Zou, Y Chen, Z Duan, H Zhang, C Pan. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012; 19(2): e18–e25
https://doi.org/10.1111/j.1365-2893.2011.01492.x pmid: 22239517
30 E Wiseman, MA Fraser, S Holden, A Glass, BL Kidson, LG Heron, MW Maley, A Ayres, SA Locarnini, MT Levy. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust 2009; 190(9): 489–492
pmid: 19413519
31 W Yi, CQ Pan, J Hao, Y Hu, M Liu, L Li, D Liang. Risk of vertical transmission of hepatitis B after amniocentesis in HBs antigen-positive mothers. J Hepatol 2014; 60(3): 523–529
https://doi.org/10.1016/j.jhep.2012.11.008 pmid: 24269471
32 GR Han, MK Cao, W Zhao, HX Jiang, CM Wang, SF Bai, X Yue, GJ Wang, X Tang, ZX Fang. 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
https://doi.org/10.1016/j.jhep.2011.02.032 pmid: 21703206
33 H Zhang, CQ Pan, Q Pang, R Tian, M Yan, X Liu. Telbivudine or lamivudine use in late pregnancy safely reduce perinatal transmission of hepatitis B virus in real-life practice. Hepatology 2014; [Accepted Article ]
https://doi.org/10.1002/hep.27034
34 CQ Pan, HB Zou, Y Chen, X Zhang, H Zhang, J Li, Z Duan. 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
https://doi.org/10.1016/j.cgh.2013.04.026 pmid: 23639606
35 ZH Han, LH Zhong, J Wang, QL Zhao, YG Sun, LW Li, LH Cao, XC Hao, H Zhuang. 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)
pmid: 17637304
36 C Lee, Y Gong, J Brok, EH Boxall, C Gluud. 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
https://doi.org/10.1136/bmj.38719.435833.7C pmid: 16443611
37 VC Wong, AK Lee, HM Ip. 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
https://doi.org/10.1111/j.1471-0528.1980.tb04458.x pmid: 7437368
38 RP Beasley, CE Stevens, IS Shiao, HC Meng. Evidence against breast-feeding as a mechanism for vertical transmission of hepatitis B. Lancet 1975; 306 (7938): 740–741
https://doi.org/10.1016/S0140-6736(75)90724-2 pmid: 52772
39 JB Hill, JS Sheffield, MJ Kim, JM Alexander, B Sercely, GD Wendel. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet Gynecol 2002; 99(6): 1049–1052
https://doi.org/10.1016/S0029-7844(02)02000-8 pmid: 12052598
40 KK Van Rompay, M Hamilton, B Kearney, N Bischofberger. Pharmacokinetics of tenofovir in breast milk of lactating rhesus macaques. Antimicrob Agents Chemother 2005; 49(5): 2093–2094
https://doi.org/10.1128/AAC.49.5.2093-2094.2005 pmid: 15855535
41 L Zhang, X Gui, J Fan, B Wang, H Ji, R Yisilafu, F Li, Y Zhou, Y Tong, X Kong, P Ye, L Zong. Breast feeding and immunoprophylaxis efficacy of mother-to-child transmission of hepatitis B virus. J Matern Fetal Neonatal Med 2014; 27(2): 182–186
https://doi.org/10.3109/14767058.2013.806901 pmid: 23682864
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