HBsAg阳性孕妇妊娠晚期富马酸丙酚替诺福韦应用背景下母体病毒学状态与新生儿anti-HBs应答关系的观察性研究-东南大学学报医学版

HBsAg阳性孕妇妊娠晚期富马酸丙酚替诺福韦应用背景下母体病毒学状态与新生儿anti-HBs应答关系的观察性研究

单位：1. 南阳市中心医院感染性疾病二病区, 河南南阳 473000;
2. 南阳市中心医院感染性疾病ICU病区, 河南南阳 473000

分类号：R722.139;R512.62

出版年·卷·期（页码）：2026·45·第四期（639-646）

摘要：

目的:观察HBsAg阳性孕妇妊娠晚期富马酸丙酚替诺福韦(tenofovir alafenamide fumarate,TAF)联合新生儿乙型肝炎人免疫球蛋白(hepatitis B immune globulin,HBIG)及乙型肝炎疫苗标准免疫方案后的乙型肝炎病毒(hepatitis B virus,HBV)母婴传播阻断结果,并探索母体乙型肝炎e抗原(hepatitis B virus e antigen,HBeAg)状态、分娩时HBV DNA水平与新生儿乙型肝炎表面抗体(antibody to HbsAg,anti-HBs)应答的关系。方法:选择2023年1月至2025年1月在本院产科接收产检并分娩的120例HBsAg阳性孕妇及其新生儿作为研究对象。根据治疗前HBV DNA水平,将HBV DNA≥2×10⁵ IU·mL^-1的90例孕妇作为主要分析集;HBV DNA＜2×10⁵ IU·mL^-1的30例孕妇仅作为真实世界补充描述。所有孕妇经临床医师综合评估后,于孕26~28周开始口服TAF至分娩。新生儿出生后12 h内注射100 IU HBIG,并按照0、1、6月龄程序接种乙型肝炎疫苗。检测孕妇治疗前及分娩时HBV DNA载量、HBeAg状态,并检测新生儿出生时及7月龄时HBV血清学标志物和anti-HBs定量。记录母婴阻断成功率、新生儿anti-HBs阳性率和几何平均浓度(geometric mean concentration,GMC)。结果:120例孕妇HBV DNA载量中位数由治疗前的5.6×10⁶ IU·mL^-1下降至分娩时的2.1×10² IU·mL^-1,107例(89.2%)孕妇分娩时HBV DNA载量＜1×10³ IU·mL^-1。随访至7月龄,母婴阻断成功率为98.3%(118/120)。主要分析集中,母婴阻断成功率为97.8%(88/90);低病毒载量补充描述病例中,母婴阻断成功率为100%(30/30)。2例阻断失败的新生儿母亲均为HBeAg阳性、治疗前HBV DNA载量＞1×10³ IU·mL^-1且分娩时HBV DNA载量仍≥1×10³ IU·mL^-1。新生儿7月龄时anti-HBs总阳性率为95.8%(115/120),anti-HBs总体GMC为487.3 mIU·mL^-1。探索性分析显示,母体HBeAg阴性且分娩时HBV DNA载量＜1×10³ IU·mL^-1的新生儿anti-HBs水平较高。多因素分析显示,母体HBeAg阳性和分娩时HBV DNA载量≥1×10³ IU·mL^-1均与新生儿7月龄lg(anti-HBs)水平降低独立相关。结论:妊娠晚期TAF联合新生儿标准免疫方案在本研究人群中观察到较高的母婴阻断成功率。母体HBeAg状态及分娩时HBV DNA水平可能与新生儿anti-HBs应答强度相关。这些结论基于TAF应用背景下的真实世界观察性资料,不能用于判断TAF相对于第一代替诺福韦或单纯标准免疫方案的比较优势。

Objective: To evaluate the efficacy of tenofovir alafenamide fumarate(TAF) initiated in late pregnancy combined with neonatal hepatitis B immune globulin(HBIG) and standard hepatitis B vaccination for blocking hepatitis B virus(HBV) mother-to-child transmission(MTCT) in HBsAg-positive pregnant women, and to explore whether maternal hepatitis B e antigen(HBeAg) serostatus and HBV DNA levels at delivery correlate with neonatal anti-hepatitis B surface antigen(anti-HBs) immune responses. Methods: This single-center, single-arm real-world observational cohort study enrolled 120 HBsAg-positive pregnant women and their newborn infants. Participants were stratified by baseline HBV DNA levels: 90 women with baseline HBV DNA ≥2×10⁵ IU·mL^-1 formed the primary cohort, and the remaining 30 women with baseline HBV DNA <2×10⁵ IU·mL^-1 constituted a supplementary low-viral-load subgroup. All eligible women received oral TAF starting at gestational weeks 26-28 until delivery following clinical assessment. All neonates were administered 100 IU HBIG within 12 hours of birth and completed the standard 0-1-6-month hepatitis B vaccination series. Maternal HBV DNA and HBeAg status were tested at baseline and delivery. Neonatal HBV serological markers and quantitative anti-HBs titers were measured at birth and at 7 months of age. Results: The mean maternal HBV DNA level declined from 5.6×10⁶ IU·mL^-1 at baseline to 2.1×10² IU·mL^-1 at delivery; 107 women(89.2%) achieved an intrapartum HBV DNA level <1×10³ IU·mL^-1. At the 7-month follow-up, the overall MTCT blockage rate was 98.3%(118/120), with rates of 97.8%(88/90) in the primary cohort and 100%(30/30) in the low-viral-load subgroup. The two cases of prophylaxis failure occurred in infants born to HBeAg-positive mothers who had baseline HBV DNA>1×10⁷ IU·mL^-1 and sustained HBV DNA ≥1×10³ IU·mL^-1 at delivery. At 7 months of age, the overall anti-HBs seropositivity rate was 95.8%(115/120), and the geometric mean concentration(GMC) of anti-HBs was 487.3 mIU·mL^-1. Exploratory analyses showed that infants delivered by HBeAg-negative mothers with intrapartum HBV DNA<1×10³ IU·mL^-1 exhibited significantly higher anti-HBs titers. Multivariable linear regression revealed that maternal HBeAg positivity and intrapartum HBV DNA ≥1×10³ IU·mL^-1 were independently associated with lower log₁₀-transformed anti-HBs levels at 7 months of age. Conclusion: TAF administered in late pregnancy combined with standardized neonatal immunoprophylaxis achieves a high MTCT blockage rate in this real-world cohort. Maternal HBeAg serostatus and intrapartum HBV DNA levels independently predict the magnitude of neonatal anti-HBs immune responses. Notably, the absence of a parallel control group limits comparative efficacy interpretations; these findings should only be regarded as real-world observational data for TAF-based MTCT prophylaxis.

参考文献：

[1] VERONESE P,DODI I,ESPOSITO S,et al.Prevention of vertical transmission of hepatitis B virus infection[J].World J Gastroenterol,2021,27(26):4182-4193.
[2] FUNK A L,LU Y,YOSHIDA K,et al.Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus:a systematic review and meta-analysis[J].Lancet Infect Dis,2021,21(1):70-84.
[3] 王爱玲,王潇滟,王前,等.中国消除艾滋病、梅毒和乙肝母婴传播评估实践[J].中国艾滋病性病,2025,31(9):928-930.
[4] 中国医师协会感染科医师分会,中华医学会感染病学分会.中国乙型肝炎病毒母婴传播防治指南(2024年版)[J].中华传染病杂志,2024,42(7):385-394.
[5] 薛莉莉,陈丽平,蒋玲玲,等.联合免疫阻断乙肝病毒母婴传播后儿童HBV感染的危险因素及预测模型构建[J].中华医院感染学杂志,2024,34(1):108-111.
[6] 中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2022年版)[J].中华肝脏病杂志,2022,30(12):1309-1331.
[7] 梁蘅恺,韦璐,苏明华,等.高病毒载量慢性乙型肝炎孕妇口服核苷(酸)类抗病毒药母婴阻断的有效性和安全性[J].肝脏,2023,28(3):296-298,308.
[8] 熊霞鹂,周鑫,朱云霞,等.富马酸丙酚替诺福韦与替诺福韦二吡呋酯阻断HBV母婴传播有效性和安全性研究[J].实用肝脏病杂志,2025,28(2):182-185.
[9] CUI F,WOODRING J,CHAN P,et al.Considerations of antiviral treatment to interrupt mother-to-child transmission of hepatitis B virus in China[J].Int J Epidemiol,2018,47(5):1529-1537.
[10] TAO Y,WU D,ZHOU L,et al.Present and future therapies for chronic hepatitis B[M]//Hepatitis B virus infection.Singapore:Springer Singapore,2019:137-186.
[11] CHIEN R N,LIAW Y F.Current trend in antiviral therapy for chronic hepatitis B[J].Viruses,2022,14(2):434.
[12] 孔泉,陈肖肖,钱姣,等.HBeAg阳性孕妇乙型肝炎知晓率现况及抗病毒治疗影响因素分析[J].东南大学学报(医学版),2025,44(2):212-220.
[13] 来国红,孙岳琴,袁茶娟,等.HBV感染孕妇阻断宫内传播失败的影响因素[J].中华医院感染学杂志,2023,33(2):257-260.
[14] 李双玲,刘丽,陈艺,等.富马酸丙酚替诺福韦与恩替卡韦治疗高血清病毒载量的代偿期乙型肝炎肝硬化患者效果比较研究[J].实用肝脏病杂志,2024,27(5):749-752.
[15] 卞成蓉,刘超,宋英伟,等.300例HBsAg阳性产妇对新生儿乙肝血清学模式和HBV DNA的影响及临床意义[J].标记免疫分析与临床,2020,27(11):1852-1856,1861.
[16] 刘淑媛,杜敬佩,祝金冉,等.HBV孕妇注射乙肝免疫球蛋白阻断HBV母婴垂直传播的被动免疫机制[J].中国妇幼保健,2015,30(21):3570-3572.
[17] 杨敏,李红梅,张雷,等.HBV高载量孕妇孕期抗病毒治疗结合标准阻断措施阻断母婴传播效果[J].中国计划生育学杂志,2024,32(5):1153-1157.
[18] 李淑,陈艳.经不同NAs治疗的慢性乙型肝炎患者HBV RNA的变化及差异[J].现代医学,2025,53(12):1858-1863.
[19] 孙美玲,郑威,张小玲.乙肝孕妇母乳喂养量表编制与信效度评定[J].现代医学,2021,49(10):1172-1176.

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