Abstract
Introduction: infection by the hepatitis B virus represents an important worldwide public health problem, since it generates a large burden of morbidity and mortality related to cirrhosis and hepatocellular carcinoma. In areas of high prevalence, vertical transmission is a major source of infection. Objective: to review the presentation of the infection by the Hepatitis B virus during pregnancy and offer guidelines to treat this entity. Search methodology: a bibliographic search was made through Pubmed, LILACS and SciELO databases, and Google Scholar search engine, of articles published until august 2017, using the terms hepatitis B virus AND infection AND pregnancy. The search was restricted to articles of the last fifteen years, in english and spanish, including review articles, controlled clinical trials and meta-analysis. A total of 535 articles were obtained for review, from which 52 were referenced. Results: children from seropositive mothers for the surface antigen of hepatitis B should receive immunoglobulin and vaccination against hepatitis B in the first twelve hours after birth, reducing the vertical transmission rate from more than 90% to less than 10%. Antiviral therapy on the third gestational trimester can prevent immunoprophylactic failure, and should be used on mothers at high risk of vertical transmission. Recent data point towards tenofovir’s safety during pregnancy, being the treatment of choice. Conclusions: universal screening on pregnant women for the hepatitis B virus infection is a cost-effective measure to reduce vertical transmission. High hepatitis B virus surface antigen levels and mother’s viral load, as well as antigen e presence, are associated with increased risk of vertical transmission. The combination of hepatitis B immunoglobulin and vaccination, given before twelve hours after birth, are associated to a reduction of the vertical transmission rate. Tenofovir is the best treatment option as antiviral therapy initiated on gestational weeks 28-32 in pregnant women at high risk of infection transmission.MÉD.UIS. 2018;31(2):49-56.
References
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6. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107.
7. Tran TT. Hepatitis B in Pregnancy. Clin Infect Dis. 2016;62(4):314–17.
8. Kubo A, Shlager L, Marks AR, Lakritz D, Colette Beaumont, Gabellini K, et al. Prevention of Vertical Transmission of Hepatitis B: An Observation Study. Ann Intern Med. 2014;160(12):828–35.
9. Chamroonkul N, Piratvisuth T. Hepatitis B During Pregnancy in Endemic Areas: Screening, Treatment, and Prevention of Motherto-Child Transmission. Pediatr Drugs. 2017;19(3):173–81.
10. Dionne-odom J, Tita A, Silverman NS. Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214(1):6–14.
11. Kar P, Mishra S. Management of hepatitis B of during pregnacy. Expert Opin Pharmacother. 2016;17(3):301–10.
12. Ter MJ, Leemans WF, De Man RA, Janssen HLA. Exacerbation of chronic hepatitis B infection after delivery. J Viral Hepat. 2008;15(1):37–41.
13. Patton H, Tran TT. Management of hepatitis B during pregnancy. Nat Rev Gastroenterol Hepatol. 2014;11(7):402–9.
14. Pol S, Corouge M, Fontaine H. Hepatitis B virus infection and pregnancy. Clin Res Hepatol Gastroenterol. 2011;35(10):618–22.
15. Castillo E, Murphy K. Hepatitis B and Pregnancy. J Obs Gynecol.2017;39(3):181–90.
16. Liu C-P, Zeng Y-L, Zhou M, Chen L-L, Hu R, Wang L, et al. Factors associated with mother-to-child transmission of hepatitis B virus despite immunoprophylaxis. Intern Med. 2015;54(7):711–6.
17. Wen WH, Chang MH, Zhao LL, Ni YH, Hsu HY, Wu JF, et al. Motherto-infant transmission of hepatitis B virus infection: Significance of maternal viral load and strategies for intervention. J Hepatol.2013;59(1):24–30.
18. Lu L-L, Chen B-X, Wang J, Wang D, Ji Y, Yi H-G, et al. Maternal transmission risk and antibody levels against hepatitis B virus e antigen in pregnant women. Int J Infect Dis. 2014;28:41–4.
19. 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):18–25.
20. Ott J, Stevens G, Wiersma S. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen (HBeAg) prevalence estimates for all world regions. BMC Infect Dis. 2012;12(12):131.
21. Wu Q, Huang H, Sun X, Pan M, He Y, Tan S, et al. Telbivudine Prevents Vertical Transmission of Hepatitis B Virus From Women With High Viral Loads: A Prospective Long-Term Study. Clin Gastroenterol Hepatol. 2015;13(6):1170–6.
22. Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med. 2016;374(24):2324–34.
23. Deng M, Zhou X, Gao S, Yang S-G, Wang B, Chen H-Z, et al. The effects of telbivudine in late pregnancy to prevent intrauterine transmission of the hepatitis B virus: a systematic review and meta-analysis. Virol J. Virology Journal. 2012;9(185):1–13.
24. Shao Z, Al Tib M, Wakim-Fleming J. Update on viral hepatitis in pregnancy. Cleve Clin J Med. 2017;84(3):202–6.
25. Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigenpositive mothers. Cochrane database Syst Rev. 2006;(2):1–107.
26. Beasley RP, Hwang LY, Lee GC, Lan CC, Roan CH, Huang FY, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet. 1983;12(8359):1099–102.
27. Li XM, Shi MF, Yang YB, Shi ZJ, Hou HY, Shen HM, et al. Effect of hepatitis B immunoglobulin on interruption of HBV intrauter ineinfection. World J Gastroenterol. 2004;10(21):3215–7.
28. Yuan J, Lin J, Xu A, Li H, Hu B, Chen J, et al. Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: A single-centre randomized study. J Viral Hepat. 2006;13(9):597–604.
29. Ac E, Gu E, Ua E, Xia Y, Liu J. Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus. Cochrane Database Syst Rev. 2017;(2):1–103.
30. Pan CQ, Duan ZP, Bhamidimarri KR, Zou HBIN, Liang XF, Li JIE. An Algorithm for Risk Assessment and Intervention of Mother to Child. Clin Gastroenterol Hepatol. 2012;10(5):452–9.
31. Brown RS, McMahon BJ, Lok ASF, Wong JB, Ahmed AT, Mouchli MA, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology. 2016;63(1):319–33.
32. Wang W, Wang J, Dang S, Zhuang G. Cost-effectiveness of antiviral therapy during late pregnancy to prevent perinatal transmission of hepatitis B virus. PeerJ. 2016;24(4):1–19.
33. Sarkar M, Terrault NA. Ending vertical transmission of hepatitis B: The third trimester intervention. Hepatology. 2014;60(2):448–51.
34. Chang CY, Aziz N, Poongkunran M, Javaid A, Trinh HN, Lau D, et al. Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B. Am J Gastroenterol. 2016;111(10):1–6.
35. Giles M, Visvanathan K, Lewin S, Bowden S, Locarnini S, Spelman T, et al. Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Gut. 2014;64(11):1810–5.
36. Wen WH, Huang CW, Chie WC, Yeung CY, Zhao LL, Lin WT, et al. Quantitative maternal hepatitis B surface antigen predicts maternally transmitted hepatitis B virus infection. Hepatology. 2016;64(5):1451–61.
37. Zonneveld M, Nunen A, Niesters HGM, Man R., Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat. 2003;10(4):294–7.
38. Ayres A, Yuen L, Jackson KM, Manoharan S, Glass A, Maley M, et al. 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(11):809–17.
39. Han GR, Cao MK, Zhao W, Jiang HX, Wang CM, Bai SF, 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. European Association for the Study of the Liver. 2011;55(6):1215–21.
40. Jaffe A, Brown RS. A Review of Antiviral Use for the Treatment of Chronic Hepatitis B Virus Infection in Pregnant Women. Gastroenterol Hepatol (N Y). 2017;13(3):154–63.
41. Seifer M, Patty A, Serra I, Li B, Standring DN. Telbivudine, a nucleoside analog inhibitor of HBV polymerase, has a different in vitro cross-resistance profile than the nucleotide analog inhibitors adefovir and tenofovir. Antiviral Res. 2009;81(2):147–55.
42. Chen J, Liao Z, Huang F, Su RK, Wang W, Cheng X, et al. Efficacy and safety of tenofovir disoproxil fumarate in preventing vertical transmission of hepatitis B in pregnancies with high viral load. Sci Rep. Springer US; 2017;7(1):4132.
43. Jourdain G, Ngo-Giang-Huong N, Cressey TR, Hua L, Harrison L, Tierney C, et al. Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus . BMC Infect Dis. BMC Infectious Diseases; 2016;16:393.
44. Hill J, Sheffield J, Kim J E. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Gynecol Obs. 2002;99(6):1049–52. 45. Shi Z. Breastfeeding of Newborns by Mothers Carrying Hepatitis B Virus. Arch Pediatr Adolesc Med. 2011;165(9):837.
46. The American Academy of Pediatrics. Breastfeeding and the Use of Human Milk. Pediatrics. 2012;129(3):827–41.
47. Benaboud S, Pruvost A, Coffie PA, Ekouévi DK, Urien S, Arrivé E, et al. Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Côte d’Ivoire, in the ANRS 12109 TEmAA Study, step 2. Antimicrob Agents Chemother. 2011;55(3):1315–7.
48. Brown RS, Verna EC, Pereira MR, Tilson HH, Aguilar C, Leu CS, et al. Hepatitis B virus and human immunodeficiency virus drugs in pregnancy: Findings from the Antiretroviral Pregnancy Registry. J Hepatol. 2012;57(5):953–9.
49. Ayoub WS, Cohen E. Review Article Hepatitis B Management in the Pregnant Patient: An Update. J Clin Transl Hepatol. 2016;4(1):241–7.
50. Hu Y, Chen J, Wen J, Xu C, Zhang S, Xu B, et al. Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus. BMC Pregnancy Childbirth. BMC Pregnancyand Childbirth; 2013;13(1):119.
51. Yang J, Zeng X, Men Y, Zhao L. Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus – a systematic review. Virol J. 2008;5:100.
52. Visvanathan K, Dusheiko G, Giles M, Wong ML, Phung N, Walker S, et al. Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders. Gut. 2016;65(2):340–50.
2. Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, et al. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-398
3. World Health Organizaton. Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. Guidel Prev Care Treat Pers with Chronic Hepat B Infect [Internet]. 2015 [citado el ]. Disponible en: http://apps.who.int/iris/bitstream/handle/10665/154590/9789241549059_eng.pdf;jsessionid=769197BF35F15E266EABE3B375BFAE49?sequence=1
4. Terrault NA, Bzowej NH, Chang K-M, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2015;63(1):261–83.
5. Association E. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. European Association for the Study of the Liver; 2012;57(1):167–85.
6. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107.
7. Tran TT. Hepatitis B in Pregnancy. Clin Infect Dis. 2016;62(4):314–17.
8. Kubo A, Shlager L, Marks AR, Lakritz D, Colette Beaumont, Gabellini K, et al. Prevention of Vertical Transmission of Hepatitis B: An Observation Study. Ann Intern Med. 2014;160(12):828–35.
9. Chamroonkul N, Piratvisuth T. Hepatitis B During Pregnancy in Endemic Areas: Screening, Treatment, and Prevention of Motherto-Child Transmission. Pediatr Drugs. 2017;19(3):173–81.
10. Dionne-odom J, Tita A, Silverman NS. Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214(1):6–14.
11. Kar P, Mishra S. Management of hepatitis B of during pregnacy. Expert Opin Pharmacother. 2016;17(3):301–10.
12. Ter MJ, Leemans WF, De Man RA, Janssen HLA. Exacerbation of chronic hepatitis B infection after delivery. J Viral Hepat. 2008;15(1):37–41.
13. Patton H, Tran TT. Management of hepatitis B during pregnancy. Nat Rev Gastroenterol Hepatol. 2014;11(7):402–9.
14. Pol S, Corouge M, Fontaine H. Hepatitis B virus infection and pregnancy. Clin Res Hepatol Gastroenterol. 2011;35(10):618–22.
15. Castillo E, Murphy K. Hepatitis B and Pregnancy. J Obs Gynecol.2017;39(3):181–90.
16. Liu C-P, Zeng Y-L, Zhou M, Chen L-L, Hu R, Wang L, et al. Factors associated with mother-to-child transmission of hepatitis B virus despite immunoprophylaxis. Intern Med. 2015;54(7):711–6.
17. Wen WH, Chang MH, Zhao LL, Ni YH, Hsu HY, Wu JF, et al. Motherto-infant transmission of hepatitis B virus infection: Significance of maternal viral load and strategies for intervention. J Hepatol.2013;59(1):24–30.
18. Lu L-L, Chen B-X, Wang J, Wang D, Ji Y, Yi H-G, et al. Maternal transmission risk and antibody levels against hepatitis B virus e antigen in pregnant women. Int J Infect Dis. 2014;28:41–4.
19. 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):18–25.
20. Ott J, Stevens G, Wiersma S. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen (HBeAg) prevalence estimates for all world regions. BMC Infect Dis. 2012;12(12):131.
21. Wu Q, Huang H, Sun X, Pan M, He Y, Tan S, et al. Telbivudine Prevents Vertical Transmission of Hepatitis B Virus From Women With High Viral Loads: A Prospective Long-Term Study. Clin Gastroenterol Hepatol. 2015;13(6):1170–6.
22. Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med. 2016;374(24):2324–34.
23. Deng M, Zhou X, Gao S, Yang S-G, Wang B, Chen H-Z, et al. The effects of telbivudine in late pregnancy to prevent intrauterine transmission of the hepatitis B virus: a systematic review and meta-analysis. Virol J. Virology Journal. 2012;9(185):1–13.
24. Shao Z, Al Tib M, Wakim-Fleming J. Update on viral hepatitis in pregnancy. Cleve Clin J Med. 2017;84(3):202–6.
25. Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigenpositive mothers. Cochrane database Syst Rev. 2006;(2):1–107.
26. Beasley RP, Hwang LY, Lee GC, Lan CC, Roan CH, Huang FY, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet. 1983;12(8359):1099–102.
27. Li XM, Shi MF, Yang YB, Shi ZJ, Hou HY, Shen HM, et al. Effect of hepatitis B immunoglobulin on interruption of HBV intrauter ineinfection. World J Gastroenterol. 2004;10(21):3215–7.
28. Yuan J, Lin J, Xu A, Li H, Hu B, Chen J, et al. Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: A single-centre randomized study. J Viral Hepat. 2006;13(9):597–604.
29. Ac E, Gu E, Ua E, Xia Y, Liu J. Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus. Cochrane Database Syst Rev. 2017;(2):1–103.
30. Pan CQ, Duan ZP, Bhamidimarri KR, Zou HBIN, Liang XF, Li JIE. An Algorithm for Risk Assessment and Intervention of Mother to Child. Clin Gastroenterol Hepatol. 2012;10(5):452–9.
31. Brown RS, McMahon BJ, Lok ASF, Wong JB, Ahmed AT, Mouchli MA, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology. 2016;63(1):319–33.
32. Wang W, Wang J, Dang S, Zhuang G. Cost-effectiveness of antiviral therapy during late pregnancy to prevent perinatal transmission of hepatitis B virus. PeerJ. 2016;24(4):1–19.
33. Sarkar M, Terrault NA. Ending vertical transmission of hepatitis B: The third trimester intervention. Hepatology. 2014;60(2):448–51.
34. Chang CY, Aziz N, Poongkunran M, Javaid A, Trinh HN, Lau D, et al. Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B. Am J Gastroenterol. 2016;111(10):1–6.
35. Giles M, Visvanathan K, Lewin S, Bowden S, Locarnini S, Spelman T, et al. Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Gut. 2014;64(11):1810–5.
36. Wen WH, Huang CW, Chie WC, Yeung CY, Zhao LL, Lin WT, et al. Quantitative maternal hepatitis B surface antigen predicts maternally transmitted hepatitis B virus infection. Hepatology. 2016;64(5):1451–61.
37. Zonneveld M, Nunen A, Niesters HGM, Man R., Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat. 2003;10(4):294–7.
38. Ayres A, Yuen L, Jackson KM, Manoharan S, Glass A, Maley M, et al. 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(11):809–17.
39. Han GR, Cao MK, Zhao W, Jiang HX, Wang CM, Bai SF, 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. European Association for the Study of the Liver. 2011;55(6):1215–21.
40. Jaffe A, Brown RS. A Review of Antiviral Use for the Treatment of Chronic Hepatitis B Virus Infection in Pregnant Women. Gastroenterol Hepatol (N Y). 2017;13(3):154–63.
41. Seifer M, Patty A, Serra I, Li B, Standring DN. Telbivudine, a nucleoside analog inhibitor of HBV polymerase, has a different in vitro cross-resistance profile than the nucleotide analog inhibitors adefovir and tenofovir. Antiviral Res. 2009;81(2):147–55.
42. Chen J, Liao Z, Huang F, Su RK, Wang W, Cheng X, et al. Efficacy and safety of tenofovir disoproxil fumarate in preventing vertical transmission of hepatitis B in pregnancies with high viral load. Sci Rep. Springer US; 2017;7(1):4132.
43. Jourdain G, Ngo-Giang-Huong N, Cressey TR, Hua L, Harrison L, Tierney C, et al. Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus . BMC Infect Dis. BMC Infectious Diseases; 2016;16:393.
44. Hill J, Sheffield J, Kim J E. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Gynecol Obs. 2002;99(6):1049–52. 45. Shi Z. Breastfeeding of Newborns by Mothers Carrying Hepatitis B Virus. Arch Pediatr Adolesc Med. 2011;165(9):837.
46. The American Academy of Pediatrics. Breastfeeding and the Use of Human Milk. Pediatrics. 2012;129(3):827–41.
47. Benaboud S, Pruvost A, Coffie PA, Ekouévi DK, Urien S, Arrivé E, et al. Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Côte d’Ivoire, in the ANRS 12109 TEmAA Study, step 2. Antimicrob Agents Chemother. 2011;55(3):1315–7.
48. Brown RS, Verna EC, Pereira MR, Tilson HH, Aguilar C, Leu CS, et al. Hepatitis B virus and human immunodeficiency virus drugs in pregnancy: Findings from the Antiretroviral Pregnancy Registry. J Hepatol. 2012;57(5):953–9.
49. Ayoub WS, Cohen E. Review Article Hepatitis B Management in the Pregnant Patient: An Update. J Clin Transl Hepatol. 2016;4(1):241–7.
50. Hu Y, Chen J, Wen J, Xu C, Zhang S, Xu B, et al. Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus. BMC Pregnancy Childbirth. BMC Pregnancyand Childbirth; 2013;13(1):119.
51. Yang J, Zeng X, Men Y, Zhao L. Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus – a systematic review. Virol J. 2008;5:100.
52. Visvanathan K, Dusheiko G, Giles M, Wong ML, Phung N, Walker S, et al. Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders. Gut. 2016;65(2):340–50.
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