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乙型肝炎与妊娠

Authors
Hannah Lee, MD
Anna SF Lok, MD
Section Editors
Rafael Esteban, MD
Louise Wilkins-Haug, MD, PhD
Deputy Editor
Jennifer Mitty, MD, MPH
Translators
伊诺, 副主任医师

引言

妊娠期间的乙型肝炎，对母亲和胎儿都带来了独特的管理问题。这些问题包括乙型肝炎病毒(hepatitis B virus, HBV)对母亲和胎儿健康的影响、妊娠对HBV感染病程的影响、妊娠期间HBV的治疗，以及预防围产期传播。由于HBV垂直传播是世界上大约一半慢性HBV感染的原因，所以预防围产期传播是全球共同努力以减少慢性HBV负荷工作中的一个重要组成部分。 (参见“乙型肝炎病毒感染的流行病学、传播和预防”)

罹患慢性HBV感染的风险与暴露于HBV时的年龄成反比。在出生时即暴露于HBV的个体，感染风险高达90%，而在儿童时期暴露于HBV的个体，感染风险要低得多(约20%-30%)。母亲筛查程序和普遍的疫苗接种已显著降低了病毒传播率。识别有风险的母亲可采取针对病毒传播的预防措施，这可将传播率从90%降低至5%-10%。预防的方法，以及尽管进行了预防仍出现病毒传播的危险因素，将在下文进一步介绍。

HBV感染对母亲的影响

对妊娠结局的影响

急性HBV感染 — 急性病毒性肝炎是妊娠期黄疸的最常见原因[1]。其他原因包括妊娠相关的急性肝脏疾病，如妊娠期急性脂肪肝、HELLP综合征和妊娠期肝内胆汁淤积(见相应专题)。

妊娠期间的急性HBV感染通常不严重，也不会增加死亡率或致畸性[1,2]。因此，妊娠期间的HBV感染不应提示考虑终止妊娠。然而，有报道称，有急性HBV感染的母亲生育低出生体重儿和早产儿的发生率增加[2,3]。此外，妊娠早期发生急性HBV感染时，围产期HBV传播率为10%[3]。如果急性感染发生于分娩时或接近分娩时，则传播率显著增加，据报道高达60%[1]。

妊娠期急性感染的治疗主要是支持治疗。应该监测患者的肝脏生化检查指标和凝血酶原时间。通常没有必要进行抗病毒治疗，除非母亲出现急性肝衰竭或迁延的严重肝炎[4](参见“乙型肝炎病毒感染的临床表现与自然病程”，关于‘急性肝炎’一节)。在这种情况下，拉米夫定(100mg/d)是合理的选择，因为拉米夫定已安全地用于妊娠期，且预期治疗持续时间较短[5]。替比夫定或替诺福韦[美国食品药品监督管理局(Food and Drug Administration, FDA)的妊娠安全性分级为B级]也是可以接受的替代选择。 (参见下文‘妊娠期间的抗病毒治疗’)

                         

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Literature review current through: 2017-06 . | This topic last updated: 2017-02-04.
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References
Top
  1. Sookoian S. Liver disease during pregnancy: acute viral hepatitis. Ann Hepatol 2006; 5:231.
  2. Hieber JP, Dalton D, Shorey J, Combes B. Hepatitis and pregnancy. J Pediatr 1977; 91:545.
  3. Jonas MM. Hepatitis B and pregnancy: an underestimated issue. Liver Int 2009; 29 Suppl 1:133.
  4. Degertekin B, Lok AS. Indications for therapy in hepatitis B. Hepatology 2009; 49:S129.
  5. Potthoff A, Rifai K, Wedemeyer H, et al. Successful treatment of fulminant hepatitis B during pregnancy. Z Gastroenterol 2009; 47:667.
  6. Lao TT, Chan BC, Leung WC, et al. Maternal hepatitis B infection and gestational diabetes mellitus. J Hepatol 2007; 47:46.
  7. Lao TT, Tse KY, Chan LY, et al. HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women. Diabetes Care 2003; 26:3011.
  8. Lobstein S, Faber R, Tillmann HL. Prevalence of hepatitis B among pregnant women and its impact on pregnancy and newborn complications at a tertiary hospital in the eastern part of Germany. Digestion 2011; 83:76.
  9. Connell LE, Salihu HM, Salemi JL, et al. Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes. Liver Int 2011; 31:1163.
  10. Tan HH, Lui HF, Chow WC. Chronic hepatitis B virus (HBV) infection in pregnancy. Hepatol Int 2008; 2:370.
  11. Söderström A, Norkrans G, Lindh M. Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission. Scand J Infect Dis 2003; 35:814.
  12. Rawal BK, Parida S, Watkins RP, et al. Symptomatic reactivation of hepatitis B in pregnancy. Lancet 1991; 337:364.
  13. Lin HH, Wu WY, Kao JH, Chen DS. Hepatitis B post-partum e antigen clearance in hepatitis B carrier mothers: Correlation with viral characteristics. J Gastroenterol Hepatol 2006; 21:605.
  14. ter Borg MJ, Leemans WF, de Man RA, Janssen HL. Exacerbation of chronic hepatitis B infection after delivery. J Viral Hepat 2008; 15:37.
  15. Yang YB, Li XM, Shi ZJ, Ma L. Pregnant woman with fulminant hepatic failure caused by hepatitis B virus infection: a case report. World J Gastroenterol 2004; 10:2305.
  16. Nguyen G, Garcia RT, Nguyen N, et al. Clinical course of hepatitis B virus infection during pregnancy. Aliment Pharmacol Ther 2009; 29:755.
  17. Shaheen AA, Myers RP. The outcomes of pregnancy in patients with cirrhosis: a population-based study. Liver Int 2010; 30:275.
  18. Brown RS Jr, Verna EC, Pereira MR, et al. Hepatitis B virus and human immunodeficiency virus drugs in pregnancy: findings from the Antiretroviral Pregnancy Registry. J Hepatol 2012; 57:953.
  19. http://www.apregistry.com/forms/interim_report.pdf (Accessed on May 14, 2014).
  20. Han GR, Cao MK, Zhao W, 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 2011; 55:1215.
  21. Pan CQ, Han GR, Jiang HX, et al. Telbivudine prevents vertical transmission from HBeAg-positive women with chronic hepatitis B. Clin Gastroenterol Hepatol 2012; 10:520.
  22. Van Rompay KK, Durand-Gasselin L, Brignolo LL, et al. Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects. Antimicrob Agents Chemother 2008; 52:3144.
  23. Gill US, et al. Factors determining bone mineral density loss in chronic hepatitis B patients: is tenofovir disoproxil fumarate the main culprit? Gut 2011; 60:A230.
  24. Gibb DM, Kizito H, Russell EC, et al. Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial. PLoS Med 2012; 9:e1001217.
  25. Wang L, Kourtis AP, Ellington S, et al. Safety of tenofovir during pregnancy for the mother and fetus: a systematic review. Clin Infect Dis 2013; 57:1773.
  26. Viganò A, Mora S, Giacomet V, et al. In utero exposure to tenofovir disoproxil fumarate does not impair growth and bone health in HIV-uninfected children born to HIV-infected mothers. Antivir Ther 2011; 16:1259.
  27. Siberry GK, Williams PL, Mendez H, et al. Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS 2012; 26:1151.
  28. Intron-A [package insert]. Kenilworth, NJ. Schering Corporation; 1994.
  29. Trotter JF, Zygmunt AJ. Conception and pregnancy during interferon-alpha therapy for chronic hepatitis C. J Clin Gastroenterol 2001; 32:76.
  30. Cundy KC, Sueoka C, Lynch GR, et al. Pharmacokinetics and bioavailability of the anti-human immunodeficiency virus nucleotide analog 9-[(R)-2-(phosphonomethoxy)propyl]adenine (PMPA) in dogs. Antimicrob Agents Chemother 1998; 42:687.
  31. Van Rompay KK, Hamilton M, Kearney B, Bischofberger N. Pharmacokinetics of tenofovir in breast milk of lactating rhesus macaques. Antimicrob Agents Chemother 2005; 49:2093.
  32. Benaboud S, Pruvost A, Coffie PA, et al. Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Cote d'Ivoire, in the ANRS 12109 TEmAA Study, Step 2. Antimicrob Agents Chemother 2011; 55:1315.
  33. Wong S, Chan LY, Yu V, Ho L. Hepatitis B carrier and perinatal outcome in singleton pregnancy. Am J Perinatol 1999; 16:485.
  34. Tse KY, Ho LF, Lao T. The impact of maternal HBsAg carrier status on pregnancy outcomes: a case-control study. J Hepatol 2005; 43:771.
  35. Reddick KL, Jhaveri R, Gandhi M, et al. Pregnancy outcomes associated with viral hepatitis. J Viral Hepat 2011; 18:e394.
  36. 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; 30:765.
  37. Stevens CE, Beasley RP, Tsui J, Lee WC. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975; 292:771.
  38. Xu DZ, Yan YP, Choi BC, et al. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol 2002; 67:20.
  39. Stevens CE, Toy PT, Tong MJ, et al. Perinatal hepatitis B virus transmission in the United States. Prevention by passive-active immunization. JAMA 1985; 253:1740.
  40. Chen HL, Lin LH, Hu FC, et al. Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV. Gastroenterology 2012; 142:773.
  41. Thompson ND, Perz JF, Moorman AC, Holmberg SD. Nonhospital health care-associated hepatitis B and C virus transmission: United States, 1998-2008. Ann Intern Med 2009; 150:33.
  42. Guidelines for Perinatal Care. In: American Academy of Pediatrics and American College of Obstetricians and Gynecologists, 4th ed, Washington, DC 1997. p.286.
  43. Soldan K, Ramsay M, Collins M. Acute hepatitis B infection associated with blood transfusion in England and Wales, 1991-7: review of database. BMJ 1999; 318:95.
  44. Pan C, Han GR, Zhao W, et al. Virologic factors associated with failure to passive-active immunoprophylaxis in infants with HBsAg-positive at birth. Hepatology 2011; 54:878A.
  45. Burk RD, Hwang LY, Ho GY, et al. Outcome of perinatal hepatitis B virus exposure is dependent on maternal virus load. J Infect Dis 1994; 170:1418.
  46. Li XM, Shi MF, Yang YB, et al. Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection. World J Gastroenterol 2004; 10:3215.
  47. Wiseman E, Fraser MA, Holden S, et al. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust 2009; 190:489.
  48. Wen WH, Chang MH, Zhao LL, et al. Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol 2013; 59:24.
  49. Kubo A, Shlager L, Marks AR, et al. Prevention of vertical transmission of hepatitis B: an observational study. Ann Intern Med 2014; 160:828.
  50. Lin HH, Lee TY, Chen DS, et al. Transplacental leakage of HBeAg-positive maternal blood as the most likely route in causing intrauterine infection with hepatitis B virus. J Pediatr 1987; 111:877.
  51. Ohto H, Lin HH, Kawana T, et al. Intrauterine transmission of hepatitis B virus is closely related to placental leakage. J Med Virol 1987; 21:1.
  52. Bai H, Zhang L, Ma L, et al. Relationship of hepatitis B virus infection of placental barrier and hepatitis B virus intra-uterine transmission mechanism. World J Gastroenterol 2007; 13:3625.
  53. Zhang SL, Yue YF, Bai GQ, et al. Mechanism of intrauterine infection of hepatitis B virus. World J Gastroenterol 2004; 10:437.
  54. López M, Coll O. Chronic viral infections and invasive procedures: risk of vertical transmission and current recommendations. Fetal Diagn Ther 2010; 28:1.
  55. Towers CV, Asrat T, Rumney P. The presence of hepatitis B surface antigen and deoxyribonucleic acid in amniotic fluid and cord blood. Am J Obstet Gynecol 2001; 184:1514.
  56. Ko TM, Tseng LH, Chang MH, et al. Amniocentesis in mothers who are hepatitis B virus carriers does not expose the infant to an increased risk of hepatitis B virus infection. Arch Gynecol Obstet 1994; 255:25.
  57. Chen LZ, Zhou WQ, Zhao SS, et al. A nested case-control study of maternal-neonatal transmission of hepatitis B virus in a Chinese population. World J Gastroenterol 2011; 17:3640.
  58. Song YM, Sung J, Yang S, et al. Factors associated with immunoprophylaxis failure against vertical transmission of hepatitis B virus. Eur J Pediatr 2007; 166:813.
  59. Beasley RP, Stevens CE, Shiao IS, Meng HC. Evidence against breast-feeding as a mechanism for vertical transmission of hepatitis B. Lancet 1975; 2:740.
  60. Hill JB, Sheffield JS, Kim MJ, et al. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet Gynecol 2002; 99:1049.
  61. Wang J, Zhu Q, Zhang X. Effect of delivery mode on maternal-infant transmission of hepatitis B virus by immunoprophylaxis. Chin Med J (Engl) 2002; 115:1510.
  62. Yang J, Zeng XM, Men YL, Zhao LS. Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus--a systematic review. Virol J 2008; 5:100.
  63. Shi Z, Yang Y, Ma L, et al. Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus: a systematic review and meta-analysis. Obstet Gynecol 2010; 116:147.
  64. Xu WM, Cui YT, Wang L, 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 2009; 16:94.