Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France; Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Global Hepatitis Programme, World Health Organization, Geneva, Switzerland.
Lancet Infect Dis. 2021 Jan;21(1):70-84. doi: 10.1016/S1473-3099(20)30586-7. Epub 2020 Aug 14.
To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who have a high risk of MTCT despite infant immunoprophylaxis. We aimed to determine the efficacy and safety of peripartum antiviral prophylaxis to inform the 2020 WHO guidelines.
In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, CENTRAL, CNKI, and Wanfang for randomised controlled trials and non-randomised studies of peripartum antiviral prophylaxis versus placebo or no prophylaxis, with no language restriction, published from database inception until March 28, 2019. We used search terms covering HBV, antiviral therapy, and pregnancy. We included studies that enrolled pregnant women with chronic infection with HBV who received antiviral prophylaxis anytime during pregnancy; that included any of the following antivirals: adefovir, emtricitabine, entecavir, lamivudine, telbivudine, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate; and that reported the following outcomes: MTCT, indicated by infant HBsAg positivity or HBV DNA positivity, or both, at age 6-12 months, and any infant or maternal adverse events. Two reviewers independently extracted data. Our primary endpoint was MTCT based on infant HBsAg positivity. We assessed pooled odds ratios (ORs) of the efficacy of peripartum antiviral prophylaxis to reduce the risk of MTCT. We assessed safety of prophylaxis by pooling risk differences. The protocol for the systematic review was pre-registered in PROSPERO, CRD42019134614.
Of 7463 articles identified, 595 articles were eligible for full-text review and 129 studies (in 157 articles) were included. The following antivirals were assessed in the meta-analysis: tenofovir disoproxil fumarate 300 mg (19 studies, with 1092 mothers and 1072 infants), lamivudine 100-150 mg (40 studies, with 2080 mothers and 2007 infants), and telbivudine 600 mg (83 studies, with 6036 mothers and 5971 infants). The pooled ORs for randomised controlled trials were similar, at 0·10 (95% CI 0·03-0·35) for tenofovir disoproxil fumarate, 0·16 (0·10-0·26) for lamivudine, and 0·14 (0·09-0·21) for telbivudine. The pooled ORs in non-randomised studies were 0·17 (0·10-0·29) for tenofovir disoproxil fumarate, 0·17 (0·12-0·24) for lamivudine, and 0·09 (0·06-0·12) for telbivudine. We found no increased risk of any infant or maternal safety outcomes after peripartum antiviral prophylaxis.
Peripartum antiviral prophylaxis is highly effective at reducing the risk of HBV MTCT. Our findings support the 2020 WHO recommendation of administering antivirals during pregnancy, specifically tenofovir disoproxil fumarate, for the prevention of HBV MTCT.
World Health Organization.
为了消除乙型肝炎病毒（HBV）母婴传播（MTCT），对于尽管婴儿免疫预防但仍有 MTCT 高风险的 HBV 感染孕妇，可能需要进行围产期抗病毒预防。我们旨在确定围产期抗病毒预防的疗效和安全性，以为 2020 年世卫组织指南提供信息。
在这项系统评价和荟萃分析中，我们检索了 PubMed、Embase、Scopus、CENTRAL、CNKI 和万方数据库，以查找抗病毒预防与安慰剂或无预防的随机对照试验和非随机研究，没有语言限制，发表时间从数据库成立到 2019 年 3 月 28 日。我们使用涵盖 HBV、抗病毒治疗和妊娠的搜索词。我们纳入了研究慢性 HBV 感染孕妇的研究，这些孕妇在妊娠期间任何时候接受抗病毒预防；包括以下任何一种抗病毒药物：阿德福韦酯、恩曲他滨、恩替卡韦、拉米夫定、替比夫定、替诺福韦艾拉酚胺富马酸盐和替诺福韦酯富马酸盐；并报告了以下结果：HBV MTCT，定义为婴儿 6-12 个月时 HBsAg 阳性或 HBV DNA 阳性，或两者均阳性，以及任何婴儿或产妇不良事件。两位评审员独立提取数据。我们的主要终点是根据婴儿 HBsAg 阳性判断围产期抗病毒预防的疗效。我们评估了围产期抗病毒预防降低 MTCT 风险的汇总优势比（OR）。我们通过汇总风险差异来评估预防的安全性。该系统评价的方案已在 PROSPERO 上预先注册，CRD42019134614。
在 7463 篇文章中，有 595 篇文章符合全文审查条件，有 129 项研究（在 157 篇文章中）入选。荟萃分析评估了以下抗病毒药物：替诺福韦酯富马酸盐 300mg（19 项研究，涉及 1092 位母亲和 1072 位婴儿）、拉米夫定 100-150mg（40 项研究，涉及 2080 位母亲和 2007 位婴儿）和替比夫定 600mg（83 项研究，涉及 6036 位母亲和 5971 位婴儿）。随机对照试验的汇总 OR 相似，替诺福韦酯富马酸盐为 0.10（95%CI 0.03-0.35），拉米夫定为 0.16（0.10-0.26），替比夫定为 0.14（0.09-0.21）。非随机研究的汇总 OR 分别为替诺福韦酯富马酸盐 0.17（0.10-0.29）、拉米夫定 0.17（0.12-0.24）和替比夫定 0.09（0.06-0.12）。我们没有发现围产期抗病毒预防后婴儿或产妇安全性结局风险增加。
围产期抗病毒预防在降低 HBV MTCT 风险方面非常有效。我们的发现支持 2020 年世卫组织建议在妊娠期间使用抗病毒药物，特别是替诺福韦酯富马酸盐，以预防 HBV MTCT。
世界卫生组织。
