比较8周孕期与12周围产期替诺福韦艾拉酚胺预防乙型肝炎病毒母婴传播的效果：一项多中心、前瞻性、开放标签、随机对照试验。

Expected 8-Week Prenatal vs 12-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-to-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-Label, Randomized Controlled Trial.

作者信息

Zeng Qing-Lei, Zhou Yi-Hua, Dong Xiao-Ping, Zhang Ji-Yuan, Li Guang-Ming, Xu Jiang-Hai, Chen Zhi-Min, Song Ning, Zhang Hong-Xu, Chen Ru-Yue, Lv Xue-Yan, Huang Shuo, Li Wei-Zhe, Pan Ya-Jie, Feng Ying-Hua, Li Zhi-Qin, Zhang Guo-Fan, Lin Wan-Bao, Zhang Guo-Qiang, Li Guo-Tao, Li Wei, Zeng Yan-Li, Zhang Da-Wei, Cui Guang-Lin, Lv Jun, Liu Yan-Min, Liang Hong-Xia, Sun Chang-Yu, Wang Fu-Sheng, Yu Zu-Jiang

机构信息

Department of Infectious Diseases and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Department of Experimental Medicine and Jiangsu Key Laboratory for Molecular Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu Province, China.

出版信息

Am J Gastroenterol. 2025 May 1;120(5):1045-1056. doi: 10.14309/ajg.0000000000003122. Epub 2024 Oct 9.

DOI:10.14309/ajg.0000000000003122

PMID:39382852

Abstract

INTRODUCTION

The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study.

METHODS

In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log 10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected 8 week) or to 4 weeks postpartum (expected 12 week) were randomly enrolled at a 1:1 ratio and followed until 6 months postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary end point was the safety of mothers and infants. The secondary end point was the HBV-MTCT rate of infants at the age of 7 months.

RESULTS

Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in 2 groups completed the study. Overall, TAF was well tolerated, no one discontinued the therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n = 231) and at 7 months (n = 222) was normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log 10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at the age of 7 months. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) vs 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the 2 groups had mildly elevated alanine aminotransferase levels at 3 months and 6 months postpartum, respectively ( P = 0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] vs 0% [0/120, 0%-3.1%]).

DISCUSSION

Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected 8-week prenatal duration is feasible. ClinicalTrials.gov , NCT04850950.

摘要

引言

预防乙型肝炎病毒母婴传播（HBV-MTCT）的母体抗病毒预防疗程差异很大，且尚未在随机对照研究中得到证实。

方法

在这项多中心、开放标签、随机对照试验中，符合条件的HBV DNA为5.3 - 9.0 log₁₀ IU/mL的孕妇，从妊娠33周第一天开始接受替诺福韦艾拉酚胺富马酸盐（TAF）治疗直至分娩（预期8周）或产后4周（预期12周），按1:1比例随机入组并随访至产后6个月。所有婴儿均接受标准免疫预防（乙肝免疫球蛋白和疫苗）。主要终点是母亲和婴儿的安全性。次要终点是7个月龄婴儿的HBV-MTCT率。

结果

在119例和120例意向性治疗孕妇中，115例和116例孕妇随访至分娩，两组中分别有110对和112对符合方案的母婴二元组完成研究。总体而言，TAF耐受性良好，无人因不良事件停药（0/239，0%，95%置信区间[CI] 0% - 1.6%），且分娩时无婴儿有先天性缺陷或畸形（0/231，0%，95% CI 0% - 1.6%）。婴儿出生时（n = 231）和7个月时（n = 222）的身体发育正常。此外，97.0%（224/231，95% CI 93.9% - 98.5%）的女性在分娩时HBV DNA <5.3 log₁₀ IU/mL。意向性治疗和符合方案的婴儿在7个月龄时的HBV-MTCT率分别为7.1%（17/239，95% CI 4.5% - 11.1%）和0%（0/222，95% CI 0% - 1.7%）。相比之下，两组中分别有15.1%（18/119，95% CI 9.8% - 22.7%）和18.3%（22/120，95% CI 12.4% - 26.2%）的女性在产后3个月和6个月时丙氨酸氨基转移酶水平轻度升高（P = 0.507）；值得注意的是，无人经历丙氨酸氨基转移酶突发（0% [0/119，95% CI 0% - 3.1%] 对0% [0/120，0% - 3.1%]）。