预防乙型肝炎病毒母婴传播的药物干预的有效性和安全性比

StephenW

预防乙型肝炎病毒母婴传播的药物干预的有效性和安全性比较：系统评价和网络荟萃分析
Ha T Nguyen 1 , Montarat Thavorncharoensap 2 , Toi L Phung 3 , Thunyarat Anothaisintawee 4 , Usa Chaikledkaew 2 , Abhasnee Sobhonslidsuk 5 , Pattarawalai Talungchit 6 , Nathorn Chaiyakunapruk 7 , John Attia 8 , Gareth J McKAY 9 , Amarin Thakinstian 10
隶属关系
隶属关系

    1
    玛希隆大学卫生技术评估 (MUHTA) 研究生课程，玛希隆大学，曼谷，泰国；越南胡志明市越南国立大学医学院。
    2
    玛希隆大学卫生技术评估 (MUHTA) 研究生课程，玛希隆大学，曼谷，泰国；泰国曼谷玛希隆大学药学院药学系社会和行政药学部。
    3
    玛希隆大学卫生技术评估 (MUHTA) 研究生课程，玛希隆大学，曼谷，泰国；越南河内卫生部卫生战略与政策研究所。
    4
    玛希隆大学卫生技术评估 (MUHTA) 研究生课程，玛希隆大学，曼谷，泰国；泰国玛希隆大学 Ramathibodi 医院家庭医学科。
    5
    泰国曼谷玛希隆大学拉玛蒂博迪医院医学系胃肠病学和肝病学科。
    6
    玛希隆大学卫生技术评估 (MUHTA) 研究生课程，玛希隆大学，曼谷，泰国；泰国曼谷玛希隆大学 Siriraj 医院医学院妇产科母婴医学科。
    7
    美国盐湖城犹他大学药学院药物治疗系。
    8
    纽卡斯尔大学医学与公共卫生学院和澳大利亚纽卡斯尔亨特医学研究所。
    9
    北爱尔兰贝尔法斯特女王大学医学院、牙科和生物医学学院公共卫生中心。
    10
    玛希隆大学卫生技术评估 (MUHTA) 研究生课程，玛希隆大学，曼谷，泰国；泰国曼谷玛希隆大学拉玛蒂博迪医院医学院临床流行病学和生物统计学系。

    PMID：35263648 DOI：10.1016/j.ajog.2022.02.042

抽象的

目的：本研究调查了药物干预预防乙型肝炎病毒垂直传播的有效性和安全性。

数据来源：检索到 2020 年 10 月 28 日的 Medline、Cochrane 和 Scopus 数据库。

研究资格标准：包括所有报告垂直传播乙型肝炎病毒并进行药物干预的随机对照试验。

研究评估和综合方法：使用 Cochrane Risk-of-Bias 工具第 2 版评估偏倚风险。使用基于母体乙型肝炎包膜抗原状态的分层网络荟萃分析估计治疗效果。

结果：纳入了 19 项针对乙型肝炎表面抗原和包膜抗原阳性母亲的研究。汇总表明，与单独使用疫苗相比，婴儿乙型肝炎疫苗和乙型肝炎免疫球蛋白的组合显着降低了传播风险，风险比为 0.52（95% 置信区间 0.30, 0.91）。与乙型肝炎疫苗和乙型肝炎免疫球蛋白的组合相比，仅添加母体富马酸替诺福韦酯，而不是替比夫定、拉米夫定或母体乙型肝炎免疫球蛋白，进一步降低了婴儿的传播风险，合并风险比为 0.10 (0.03, 0.35 ）。在乙型肝炎表面抗原阳性和混合、未知或阴性乙型肝炎包膜抗原状态的母亲中进行的 12 项研究提供的证据有限，表明母体乙型肝炎免疫球蛋白联合乙型肝炎疫苗和婴儿免疫球蛋白可能是最好的治疗方法，但这与婴儿乙型肝炎疫苗和免疫球蛋白的组合相比，未能达到统计学意义。同样，在疫苗接种中添加婴儿乙型肝炎免疫球蛋白可能会提供额外的益处，但再次未能达到统计学意义。

结论：乙型肝炎疫苗和免疫球蛋白联合应用于婴儿是预防母体乙型肝炎表面抗原和包膜抗原双阳性垂直传播的基石。在这种婴儿联合方案中添加母体替诺福韦被认为可能是最有效的治疗方法。对于乙型肝炎表面抗原阳性和混合、未知或阴性乙型肝炎包膜抗原状态的母亲的婴儿，除了单独的乙型肝炎疫苗外，没有其他药物可以提供更多益处。

关键词：HBIG；乙肝病毒；拉米夫定；替比夫定；替诺福韦；垂直传输。

StephenW

Comparative efficacy and safety of pharmacological interventions to prevent Mother-to-Child transmission of hepatitis B virus: A systematic review and network meta-analysis
Ha T Nguyen  1 , Montarat Thavorncharoensap  2 , Toi L Phung  3 , Thunyarat Anothaisintawee  4 , Usa Chaikledkaew  2 , Abhasnee Sobhonslidsuk  5 , Pattarawalai Talungchit  6 , Nathorn Chaiyakunapruk  7 , John Attia  8 , Gareth J McKAY  9 , Ammarin Thakkinstian  10
Affiliations
Affiliations

    1
    Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; School of Medicine, Vietnam National University Ho Chi Minh City, Vietnam.
    2
    Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Social and Administrative Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
    3
    Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Health Strategy and Policy Institute, Ministry of Health, Hanoi, Vietnam.
    4
    Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Department of Family Medicine, Ramathibodi Hospital, Mahidol University, Thailand.
    5
    Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
    6
    Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Maternal and Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
    7
    Department of Pharmacotherapy, College of Pharmacy, The University of Utah, Salt Lake City, United States.
    8
    School of Medicine and Public Health, The University of Newcastle, and Hunter Medical Research Institute, Newcastle, Australia.
    9
    Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland.
    10
    Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

    PMID: 35263648 DOI: 10.1016/j.ajog.2022.02.042

Abstract

Objectives: This study investigated the efficacy and safety of pharmacological interventions to prevent vertical transmission of hepatitis B virus.

Data source: Medline, Cochrane and Scopus databases were searched up to 28th October 2020.

Study eligibility criteria: All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacological intervention were included.

Study appraisal and synthesis methods: Risk of bias was assessed using the Cochrane Risk-of-Bias tool Version 2. Treatment efficacy was estimated using stratified network meta-analysis based on maternal hepatitis B envelope antigen status.

Results: Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated a combination of hepatitis B vaccine and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared to vaccine alone with a risk ratio of 0.52 (95% confidence interval 0.30, 0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared to a combination of hepatitis B vaccine and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03, 0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown or negative hepatitis B envelope antigen status, provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccine and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared to a combination of hepatitis B vaccine and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but again failed to reach statistical significance.

Conclusion: A combination of hepatitis B vaccine and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers double positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir in this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccine alone.

Keywords: HBIG; HBV; lamivudine; telbivudine; tenofovir; vertical transmission.

StephenW

https://www.ajog.org/article/S0002-9378(22)00170-3/pdf