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替诺福韦和安慰剂预防乙型肝炎围生期传播的比较
Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B


Gonzague Jourdain ... 其他 • 2018.03.08
相关阅读
• 妊娠期间或妊娠之后口服抗病毒药物预防乙型肝炎的垂直传播

评价替诺福韦预防乙型肝炎病毒母婴传播效果

 

闻玉梅†‡

†复旦大学上海医学院;‡教育部/卫计委医学分子病毒学实验室

 

乙型肝炎病毒感染引起的肝病是危害中国人民健康的重大疾病。乙型肝炎主要通过母婴,以及血源、性等途径传播,其中母婴垂直传播获得的感染危害最大。病毒复制高、血清HBeAg阳性的母亲可通过宫内、分娩过程或初生期接触而感染婴儿,其中65%~90%可致慢性肝炎,并可能发展为肝硬化甚至肝癌1

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摘要


背景

尽管婴儿接受乙型肝炎免疫球蛋白治疗,但乙型肝炎病毒(HBV)载量升高的孕妇仍有传播给其婴儿的风险。

 

方法

在泰国进行的这项多中心、双盲临床试验中,我们将谷丙转氨酶水平≤60 IU/L的乙型肝炎e抗原(HBeAg)阳性孕妇随机分组,使其从妊娠28周至产后2个月接受富马酸替诺福韦二吡呋酯(TDF)或安慰剂治疗。婴儿出生时接种乙型肝炎免疫球蛋白,并在出生时以及1、2、4和6月龄时接种乙型肝炎疫苗。主要终点是婴儿中乙型肝炎表面抗原(HBsAg)阳性状态,以6月龄时的HBV DNA水平确认。我们计算出,328例女性样本将为试验提供90%的检验功效来检测到传播率至少9个百分点的差异(预期传播率,TDF组3% vs.安慰剂组12%)。

 

结果

2013年1月至2015年8月,我们纳入了331例女性;其中168例被随机分配至TDF组,163例被随机分配至安慰剂组。入组时,孕龄中位数为28.3周,HBV DNA水平中位数为8.0 log10 IU/mL。在322例分娩中(参与者的97%),有319例单胎分娩、两对孪生婴儿和一例死产婴儿。从出生至乙型肝炎免疫球蛋白用药的时间中位数为1.3小时,从出生至乙型肝炎疫苗接种的时间中位数为1.2小时。在主要分析中,TDF组147例婴儿(0;95%置信区间[CI],0~2)无一受感染,而安慰剂组147例婴儿中有3例(2%;95% CI,0~6)受感染(P=0.12)。在两组之间,不良事件发生率无显著差异。在TDF组和安慰剂组中,停用试验治疗方案后,母亲谷丙转氨酶水平超过300 IU/L的发生率分别为6%和3%(P=0.29)。

 

结论

在HBeAg阳性母亲所生婴儿应用乙型肝炎免疫球蛋白和乙型肝炎疫苗后母婴HBV传播率较低的情况下,母亲额外使用TDF没有显著降低传播率(由尤尼斯·肯尼迪·施莱佛国立儿童健康与人类发展研究所[Eunice Kennedy Shriver National Institute of Child Health and Human Development]资助;在ClinicalTrials.gov注册号为NCT01745822)。





作者信息

Gonzague Jourdain, M.D., Ph.D., Nicole Ngo-Giang-Huong, Pharm.D., Ph.D., Linda Harrison, M.Sc., Luc Decker, Ph.D., Woottichai Khamduang, Ph.D., Camlin Tierney, Ph.D., Nicolas Salvadori, M.Sc., Tim R. Cressey, Ph.D., Wasna Sirirungsi, Ph.D., Jullapong Achalapong, M.D., Prapap Yuthavisuthi, M.D., Prateep Kanjanavikai, M.D., Orada P. Na Ayudhaya, M.D., Thitiporn Siriwachirachai, M.D., Sinart Prommas, M.D., Prapan Sabsanong, M.D., Aram Limtrakul, M.D., Supang Varadisai, M.D., Chaiwat Putiyanun, M.D., Pornnapa Suriyachai, M.D., Prateung Liampongsabuddhi, M.D., Suraphan Sangsawang, M.D., Wanmanee Matanasarawut, M.D., Sudanee Buranabanjasatean, M.D., Pichit Puernngooluerm, M.D., Chureeratana Bowonwatanuwong, M.D., Thanyawee Puthanakit, M.D., Virat Klinbuayaem, M.D., Satawat Thongsawat, M.D., Sombat Thanprasertsuk, M.D., George K. Siberry, M.D., Diane H. Watts, M.D., Nahida Chakhtoura, M.D., Ms.G.H., Trudy V. Murphy, M.D., Noele P. Nelson, M.D., Ph.D., M.P.H., Raymond T. Chung, M.D., Stanislas Pol, M.D., Ph.D., and Nantasak Chotivanich, M.D.
From the Institut de Recherche pour le Développement Unité Mixte Internationale 174–Program for Health, Prevention, and Treatment (PHPT) (G.J., N.N.-G.-H., L.D., N.S., T.R.C.), the Faculty of Associated Medical Sciences, Chiang Mai University (G.J., N.N.-G.-H., L.D., W.K., N.S., T.R.C., W.S.), Nakornping Hospital (A.L.), Health Promotion Center Region 1 (S.S.), the Medical Department, Sanpatong Hospital (V.K.), and the Department of Internal Medicine, Faculty of Medicine, Chiang Mai University (S. Thongsawat), Chiang Mai, the Obstetrics and Gynecology Department, Chiangrai Prachanukroh Hospital (J.A.), and Mae Chan Hospital (S.B.), Chiang Rai, Prapokklao Hospital, Chantaburi (P.Y.), Banglamung Hospital (P.K.) and Chonburi Hospital (C.B., N. Chotivanich), Chonburi, Nopparat Rajathanee Hospital (O.P.N.A.), Bhumibol Adulyadej Hospital (S. Prommas), and the Faculty of Medicine, Chulalongkorn University (T.P.), Bangkok, Khon Kaen Hospital, Khon Kaen (T.S.), Samutprakarn Hospital, Samutprakarn (P. Sabsanong), Samutsakhon Hospital, Samutsakorn (S.V.), Chiang Kham Hospital (C.P.) and Phayao Hospital (P. Suriyachai), Phayao, Lampang Hospital, Lampang (P.L.), Lamphun Hospital, Lamphun (W.M.), Maharaj Nakornratchasrima Hospital, Nakornratchasrima (P.P.), and the Department of Disease Control, Ministry of Public Health, Nonthaburi (S. Thanprasertsuk) — all in Thailand; the Department of Immunology and Infectious Diseases (G.J., N.N.-G.-H., T.R.C.) and the Center for Biostatistics in AIDS Research (L.H., C.T.), Harvard T.H. Chan School of Public Health, and the Gastrointestinal Unit, Massachusetts General Hospital (R.T.C.) — both in Boston; the Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom (T.R.C.); the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (G.K.S., N. Chakhtoura); the Office of the Global AIDS Coordinator, Department of State, Washington, DC (D.H.W.); the Centers for Disease Control and Prevention, Atlanta (T.V.M., N.P.N.); and Université Paris Descartes, INSERM Unité 1223, Institut Pasteur, the Department of Hepato-Gastroenterology, Cochin University Hospital, Paris (S. Pol). Address reprint requests to Dr. Jourdain at the Faculty of Associated Medical Sciences–PHPT, 110 Intawaroros Rd., Sripoom, Muang, Chiang Mai 50200, Thailand, or at gonzague.jourdain@ird.fr.

 

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