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中华实验和临床感染病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (05) : 303 -310. doi: 10.3877/cma.j.issn.1674-1358.2021.05.003

论著

个体化方案阻断乙型肝炎病毒母婴传播十年数据分析
张荣1, 唐雍艳1, 喻茜2, 丁志云3, 朱莉4, 姚杰1, 赵继2, 张玉1, 马德明1, 张丽娜1, 姚小英1, 丁善文1, 石尚虎1, 贾玉芳3, 沈静3, 王海燕4, 龚婵聪4, 沈秀娟4, 李明4, 钱峰4, 朱传武4,†()   
  1. 1. 215131　苏州市，苏州市第五人民医院感染产科
    2. 215300　昆山市，昆山市妇幼保健所
    3. 215300　昆山市，昆山市中医医院产科
    4. 215131　苏州市，苏州市第五人民医院肝病科
  • 收稿日期:2020-10-16 出版日期:2021-10-15
  • 通信作者: 朱传武
  • 基金资助:
    苏州市卫健委临床重点病种诊疗技术专项(No. LCZX201613); 苏州市科学技术局民生科技项目(No. SS202068)

Analysis on ten-year data of individualized programs to prevent mother-to-child transmission of hepatitis B virus

Rong Zhang1, Yongyan Tang1, Qian Yu2, Zhiyun Ding3, Li Zhu4, Jie Yao1, Ji Zhao2, Yu Zhang1, Deming Ma1, Lina Zhang1, Xiaoying Yao1, Shanwen Ding1, Shanghu Shi1, Yufang Jia3, Jing Shen3, Haiyan Wang4, Chancong Gong4, Xiujuan Shen4, Ming Li4, Feng Qian4, Chuanwu Zhu4,†()   

  1. 1. Obstetrics Department, the Fifth People’s Hospital of Suzhou, Suzhou 215131, China
    2. Kunshan Maternal and Child Health Institute, Kunshan 215300, China
    3. Obstetrics Department, Kunshan Hospital of Traditional Chinese Medicine, Kunshan 215300, China
    4. Department of Hepatology, the Fifth People’s Hospital of Suzhou, Suzhou 215131, China
  • Received:2020-10-16 Published:2021-10-15
  • Corresponding author: Chuanwu Zhu
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引用本文：

张荣, 唐雍艳, 喻茜, 丁志云, 朱莉, 姚杰, 赵继, 张玉, 马德明, 张丽娜, 姚小英, 丁善文, 石尚虎, 贾玉芳, 沈静, 王海燕, 龚婵聪, 沈秀娟, 李明, 钱峰, 朱传武. 个体化方案阻断乙型肝炎病毒母婴传播十年数据分析[J]. 中华实验和临床感染病杂志(电子版), 2021, 15(05): 303-310.

Rong Zhang, Yongyan Tang, Qian Yu, Zhiyun Ding, Li Zhu, Jie Yao, Ji Zhao, Yu Zhang, Deming Ma, Lina Zhang, Xiaoying Yao, Shanwen Ding, Shanghu Shi, Yufang Jia, Jing Shen, Haiyan Wang, Chancong Gong, Xiujuan Shen, Ming Li, Feng Qian, Chuanwu Zhu. Analysis on ten-year data of individualized programs to prevent mother-to-child transmission of hepatitis B virus[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2021, 15(05): 303-310.

目的

分析个体化方案对乙型肝炎病毒（HBV）母婴传播（MTCT）的阻断效果。

方法

苏州市第五人民医院肝病科和产科根据HBsAg阳性孕妇的HBeAg状态和HBV DNA水平，对国内肝病指南推荐的免疫阻断方案进行了优化和细化，形成了个体化免疫阻断方案。本研究收集2009年9月至2019年5月于本院分娩的所有HBsAg阳性孕妇的临床资料及其8~12月龄婴儿的HBV血清学标志物（观察组），均采用个体化方案进行MTCT阻断。同时，收集2015年2月至2019年7月于昆山市分娩的HBsAg阳性孕妇及其婴儿相应的临床和随访资料作为对照，对照组采用国内肝病指南推荐的免疫阻断方案。

结果

观察组共有2 702例孕妇入组，分娩健康新生儿2 717例（含15例双胎）。其中2 345例新生儿（含12例双胎）接受了联合免疫治疗方案（方案1和方案2）进行阻断；369例孕妇采用核苷（酸）类似物（NAs）抗病毒治疗方案（方案3），分娩新生儿372例（含3例双胎）。对照组共2 616例HBsAg阳性孕妇入组，分娩健康新生儿2 620例（含4例双胎），均接受联合免疫治疗方案进行阻断。观察组共19例婴儿HBsAg阳性，均为HBeAg阳性孕妇所产婴儿。其母亲HBV DNA载量均>5 log10IU/ml，其中> 7 log10IU/ml的孕妇占84.21%（16/19）。观察组总体母婴阻断失败率为0.70%（19/2 717），总体免疫阻断失败率为0.81%（19/2 345）。HBeAg阳性孕妇中总体阻断失败率为1.21%（19/1 574），免疫阻断失败率为1.51%（19/1 256），HBV DNA载量> 7 log10IU/ml的孕妇免疫阻断失败率为1.69%（16/949）。HBeAg阴性、HBV DNA载量< 5 log10IU/ml和应用NAs抗病毒预防治疗的孕妇，母婴阻断成功率均为100%。应用免疫阻断和NAs治疗组间母婴阻断失败率差异无统计学意义（P = 0.096）。对照组共53例婴儿HBsAg阳性，总体母婴阻断失败率为2.02%（53/2 620），显著高于观察组（χ2 = 12.733、P < 0.001）。其中，HBeAg阳性孕妇阻断失败率为2.87%（15/523），HBeAg阴性孕妇为1.81%（38/2 097），均显著高于观察组，差异均有统计学意义（χ2 = 6.790、P = 0.009，χ2 = 20.958、P < 0.001）。观察组不同分娩方式和喂养方式母婴阻断失败率差异均无统计学意义（χ2 = 0.045、P = 0.832，χ2 = 0.021、P = 0.884）。

结论

个体化方案显著提高了母婴阻断成功率；基于孕妇HBV感染状况而实施的个体化免疫预防策略，可显著降低联合免疫阻断失败率。

关键词: 肝炎病毒，乙型, 母婴传播, 个体化方案, 阻断, 效果分析
Objective

To investigate the effect of individualized programs on blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV).

Methods

Based on the status of HBeAg and HBV DNA level in HBsAg-positive pregnant women, the Department of Hepatology and Obstetrics of the Fifth People’s Hospital of Suzhou optimized and refined the immunoblocking programs recommended by the domestic guidelines for liver disease, and formed an individualized immune blocking schemes. The clinical data of all HBsAg-positive pregnant women hospitalized in our hospital from September 2009 to May 2019, and the HBV serological markers of their infants aged 8-12 months (observation group) were collected. Individualized programs were used to block MTCT of HBV. Meanwhile, the corresponding clinical and follow-up data of all HBsAg-positive pregnant women and their infants delivered in Kunshan city from February 2015 to July 2019 were collected as control group. The newborns of the control group were given the immunoprophylaxis recommended by the domestic guidelines for liver diseases.

Results

Total of 2 702 pregnant women were enrolled in observation group, and 2 717 healthy newborns (including 15 twins) were delivered. Among them, 2 345 newborns (including 12 twins) were treated with immunoprophylaxis measures (program 1 and 2); 369 pregnant women were treated with nucleos(t)ide analogs (NAs) antiviral therapy (program 3), and 372 newborns (including 3 twins) were delivered. In control group, 2 616 pregnant women with HBsAg positive were enrolled, 2 620 healthy newborns (including 4 twins) were delivered and were given immunoblocking treatment. In observation group, 19 infants were detected positive for serum HBsAg, and their mothers were all with positive HBeAg. The HBV DNA loads of their mothers were all > 5 log10IU/ml, and the women with HBV DNA level > 7 log10IU/ml accounted for 84.21% (16/19). The overall failure rate of blocking MTCT was 0.70% (19/2 717), and the overall immunoblocking failure rate was 0.81% (19/2 345). Among pregnant women with HBeAg positive, the overall failure rate was 1.21% (19/1 574), the immunoblocking failure rate was 1.51% (19/1 256), which was 1.69% (16/949) in pregnant women with HBV DNA load > 7 log10 IU/ml. For all pregnant women with negative HBeAg, HBV DNA load < 5 log10IU/ml and NAs prophylaxis, the success rate of blocking MTCT was 100%. There was no significant difference in the failure rate between the two subgroups of immunoprophylaxis and NAs therapy (P = 0.096). A total of 53 infants were serum HBsAg positive in control group. The overall immunoblocking failure rate was 2.02% (53/2 620), which was significantly higher than that of the observation group (χ2 = 12.733, P < 0.001). Among them, the failure rates were 2.87% (15/523) and 1.81% (38/2 097) in HBeAg positive and negative pregnant women, respectively, which were significantly higher than the corresponding failure rates of the observation group (χ2 = 6.790, P = 0.009; and χ2 = 20.958, P < 0.001). There was no significant difference of the failure rates between different delivery and feeding modes in observation group, respectively (χ2 = 0.045, P = 0.832; χ2 = 0.021, P = 0.884).

Conclusions

The individualized program remarkably improves the success rate of MTCT prevention for HBV. The individualized immunoprophylaxis strategy based on HBV infection of pregnant women significantly reduces the failure rate of combined immunoblocking program.

Key words: Hepatitis B virus, Mother-to-child transmission, Individualized program, Blocking, Effect analysis
图1 观察组HBV的MTCT个体化阻断方案
表1 两组孕妇不同HBeAg状态的母婴阻断失败率
组别 例数 婴儿总数[例（%）] 婴儿HBsAg阳性[例（%）] 阻断失败率（%） χ2值 P值
观察组         13.894 < 0.001
  HBeAg（+） 1 568 1 574（57.93） 19（100.00） 1.21    
  HBeAg（-） 1 134 1 143（42.07） 0（0.00） 0.00    
对照组         2.355 0.125
  HBeAg（+） 522 523（19.96） 15（28.30） 2.87    
  HBeAg（-） 2 094 2 097（80.04） 38（71.70） 1.81    
表2 HBV DNA载量> 5 log10IU/ml孕妇及其婴儿HBV DNA载量分布[例（%）]
HBV DNA载量（log10IU/ml） 孕妇 婴儿HBsAg阳性
5~6 175（13.77） 2（10.53）
6~7 150（11.80） 1（5.26）
7~8 519（40.83） 8（42.11）
8~9 419（32.97） 7（36.84）
> 9 8（0.63） 1（5.26）
合计 1 271（100.00） 19（100.00）
表3 两组孕妇不同分娩方式的母婴阻断失败率
组别 新生儿例数 婴儿HBsAg阳性[例（%）] 阻断失败率（%） χ2值 P值
观察组 2 717 19（100.00）   0.045 0.832
  阴道产 1 507 11（57.89） 0.73    
  剖宫产 1 210 8（42.11） 0.66    
对照组 2 620 53（100.00）   0.083 0.774
  阴道产 1 431 30（56.60） 2.10    
  剖宫产 1 189 23（43.40） 1.93    
表4 两组不同喂养方式孕妇的母婴阻断失败率
组别 新生儿例数 婴儿HBsAg阳性[例（%）] 阻断失败率（%） χ2值 P值
观察组 2 717 19（100.00）      
  母乳喂养 1 901 13（68.42） 0.68 0.021 0.884
  人工喂养 816 6（31.58） 0.74    
对照组 2 620 19（100.00）      
  母乳喂养 2 171 37（69.81） 1.70 6.158 0.013
  人工喂养 449 16（30.19） 3.56    
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