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中华实验和临床感染病杂志(电子版) ›› 2018, Vol. 12 ›› Issue (04) : 316 -323. doi: 10.3877/cma.j.issn.1674-1358.2018.04.002

所属专题: 文献

荟萃分析

不同干预措施预防乙型肝炎病毒母婴传播的网络Meta分析
朱晓红1, 陈智娴2, 庄勋3, 郝艳丽1, 蔡梦芝1, 秦刚1,()   
  1. 1. 226006 南通市,江苏省南通市第三人民医院肝病中心
    2. 226001 南通市,江苏省南通卫生高等职业技术学校
    3. 226019 南通市,南通大学公共卫生学院
  • 收稿日期:2017-12-31 出版日期:2018-08-15
  • 通信作者: 秦刚
  • 基金资助:
    江苏省重点研发计划(社会发展)重点病种规范化诊疗项目(No. BE2015655); 江苏省卫计委"六个一工程"科研项目(No. LGY2017039)

Comparative effectiveness of prophylactic strategies for perinatal transmission of hepatitis B virus: a network Meta-analysis of randomized controlled trials

Xiaohong Zhu1, Zhixian Chen2, Xun Zhuang3, Yanli Hao1, Mengzhi Cai1, Gang Qin1,()   

  1. 1. Center for Liver Diseases, Nantong the Third People’s Hospital, Nantong 226001, China
    2. Nantong Health College of Jiangsu Province, Nantong 226020, China
    3. School of Public Health, Nantong University, Nantong 226019, China
  • Received:2017-12-31 Published:2018-08-15
  • Corresponding author: Gang Qin
  • About author:
    Corresponding author: Qin Gang, Email:
引用本文:

朱晓红, 陈智娴, 庄勋, 郝艳丽, 蔡梦芝, 秦刚. 不同干预措施预防乙型肝炎病毒母婴传播的网络Meta分析[J/OL]. 中华实验和临床感染病杂志(电子版), 2018, 12(04): 316-323.

Xiaohong Zhu, Zhixian Chen, Xun Zhuang, Yanli Hao, Mengzhi Cai, Gang Qin. Comparative effectiveness of prophylactic strategies for perinatal transmission of hepatitis B virus: a network Meta-analysis of randomized controlled trials[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(04): 316-323.

目的

评价不同干预措施阻断乙型肝炎病毒(HBV)母婴传播的效果。

方法

通过检索国内外电子数据库自建库至2016年12月31日与预防HBV母婴传播有关的随机对照试验,4种干预HBV母婴传播的措施分别为新生儿接种乙肝疫苗(HBVac);新生儿乙肝疫苗和乙肝免疫球蛋白联合注射(HBIG + HBVac);妊娠晚期多次注射乙肝免疫球蛋白+新生儿接种乙肝疫苗和乙肝免疫球蛋白联合注射(HBIG/HBIG + HBVac),妊娠晚期抗病毒治疗+新生儿乙肝疫苗和乙肝免疫球蛋白联合注射(AVT/HBIG + HBVac)。按入选标准筛选后提取其中的数据进行直接、网络Meta分析,采用相对危险度(RR)和95%置信区间(CI)进行评估。

结果

共纳入15篇文献,Meta分析显示,HBVac处理组显著降低了HBV母婴传播机率,RR为0.32;95%CI:0.21~0.50。HBIG + HBVac处理显著优于HBVac处理,RR = 0.37,95%CI:0.2~0.67。对高病毒载量(HBV DNA ≥ 2 × 105 IU/ml)的HBV感染妊娠者,HBIG/HBIG + HBVac和AVT/HBIG + HBVac疗效显著优于HBIG + HBVac和HBVac处理(RR = 0.47,95%CI:0.29~0.75;RR = 0.31,95%CI:0.10~0.99)。

结论

妊娠期抗病毒治疗联合新生儿注射HBIG对阻断HBV母婴传播效果显著,妊娠晚期注射HBIG的母婴阻断效果尚不确切。

Objective

To evaluate the effectiveness of interventions to block mother-to-child transmission of hepatitis B virus.

Methods

References and randomized control trials (RCT) related to HBV prevention of mother-to-child transmission were collected by retrieving the domestic and foreign electronic databases (from database establishment to December 31st, 2016). The four measures to intervene in mother-to-child transmission of HBV were placebo/none, active immunoprophylaxis [hepatitis B vaccine series starting at birth (HBVac)], passive-active immunoprophylaxis [hepatitis B immunoglobulin and vaccine (HBIG + HBVac)], prenatal HBIG administration (HBIG/HBIG + HBVac), and prenatal antiviral therapy (AVT/HBIG + HBVac). According to the selection criteria, the data was extracted for direct and network Meta analysis, relative risk (RR) and 95% confidence interval (CI) were used for evaluation.

Results

Total of 15 RCTs involving infants of HBV carrier mothers were eligible for analysis. Network meta-analysis demonstrated similar results as direct comparisons. HBVac alone significantly reduced the risk of HBV infection in infants of HBV carrier mothers (RR= 0.32, 95%CI: 0.21-0.50). Effect of the combination of immunoglobulin with vaccine (HBIG + HBVac) was better than HBVac alone (RR= 0.37, 95%CI: 0.20-0.67). In pregnant women with high viral load (HBV DNA≥2 × 105IU/ml), the treatment effect of HBIG/HBIG + HBVac and AVT/HBIG + HBVac was both better than that of HBIVac and HBVac in late pregnancy (RR= 0.47, 95%CI: 0.29-0.75;RR= 0.31, 95%CI: 0.10-0.99, respectively).

Conclusions

The antiviral therapy combined with injection of HBIG was effective in blocking the transmission of HBV in pregnant women, but the effect of HBIG injection in later stages of pregnancy was not yet accurate.

图1 研究选择流程图
图2 四种HBV母婴阻断措施网络图
表1 入组随机试验资料
研究论文 研究地区 研究时间 中心 妊娠患者(HBeAg+/-) 干预措施 婴儿样本大小 传播数量 Jadad评分
妊娠患者 婴儿
Wong VC(1984) 中国 1981-1983 1 阳性 C:安慰剂 C:安慰剂 C:34 C:25 5(2+2+1)
? ? T1:安慰剂 T1:HBVac T1:35 T1:7 ?
? ? T2:安慰剂 T2:HBIG + HBVac T2:35 T2:2 ?
Lo KJ(1985) 中国 1981-1983 1 阳性 C:安慰剂 C:安慰剂 C:29 C:26 2(1+0+1)
? ? T1:安慰剂 T1:HBVac T1:38 T1:9 ?
? ? T2:安慰剂 T2:HBIG + HBVac T2:36 T2:4 ?
Farmer K(1987) 新西兰 1983-1985 1 阳性 C:安慰剂 C:HBVac C:18 C:4 2(1+0+1)
? ? T:安慰剂 T:HBIG + HBVac T:21 T:3 ?
Theppisai U(1987) 泰国 1984-1985 1 阳性 T1:安慰剂 T1:HBVac T1:18 T1:2 1(1+0+0)
? ? T2:安慰剂 T2:HBIG + HBVac T2:27 T2:0 ?
Poovorawan Y(1992) 泰国 未报道 1 阳性 C:安慰剂 C:HBVac C:59 C:2 2(1+0+1)
? ? T:安慰剂 T:HBIG + HBVac T:60 T:0 ?
Sehgal A(1992) 印度 1987-1989 1 T1:7/14 T1:安慰剂 T1:HBVac T1:21 T1:2 2(1+0+1)
? T2:7/17 T2:安慰剂 T2:HBIG + HBVac T2:24 T2:2 ?
Assateerawalt A(1993) 泰国 1988-1989 1 阳性 T1:安慰剂 T1:HBVac T1:26 T1:3 3(2+0+1)
? ? T2安慰剂 T2:HBIG + HBVac T2:23 T2:1 ?
Xu ZY(1995) 中国 1982-1989 1 未报道 C:安慰剂 C:安慰剂 C:55 C:19 4(2+2+0)
? ? T1:安慰剂 T1:HBVac T1:56 T1:10 ?
? ? T2:安慰剂 T2:HBIG + HBVac T2:27 T2:1 ?
Zhu QR(2003) 中国 1995-1999 1 C:189/304 C:安慰剂 C:HBIG + HBVac C:496 C:48 2(2+0+0)
? T:169/318 T:HBIG 200~400 U(7~9月) T:HBIG + HBVac T:491 T:19 ?
Yuan J(2006) 中国 1999-2004 1 阳性 C:安慰剂 C:HBIG + HBVac C:133 C:17 2(1+0+1)
? ? T:孕晚期(7~9月)HBIG 200~400 U T:HBIG + HBVac T:118 T:13 ?
王福彦(2008) 中国 2001-2006 1 C:60/60 C:安慰剂 C:HBIG + HBVac C:120 C:19 2(2+0+0)
? T:79/80 T:HBIG 200~400 U(7~9月) T:HBIG + HBVac T:159 T:7 ?
Xu WM(2009) 中国 未报道 7 C:61/0 C:安慰剂 C:HBIG + HBVac C:44 C:6 5(2+2+1)
? T:88/1 T:孕32周到分娩后1个月,LAM 100 mg/d T:HBIG + HBVac T:40 T:3 ?
研究论文 研究地区 研究时间 中心 妊娠患者(HBeAg+/-) 干预措施 婴儿样本大小 传播数量 Jadad评分
妊娠患者 婴儿
张丽菊(2009) 中国 2007-2008 1 未报道 C:安慰剂 T1:HBIG + HBVac C:30 C:4 1(1+0+0)
? ? T:孕28~32周到分娩后1个月,LdT 600 mg/d T2:HBIG + HBVac T:31 T:0 ?
Pande C(2013) 印度 2004-2009 1 19%阳性 C:安慰剂 C:安慰剂+ HBVac C:116 C:6 5(2+2+1)
? ? T:安慰剂 T:HBIG + HBVac T:106 T:0 ?
Pan CQ(2016) 中国 2012-2013 6 阳性 C:安慰剂 C:HBIG + HBVac C:88 C:6 3(2+0+1)
? ? T:孕30~32周到分娩后1个月,TDF 300 mg/d T:HBIG + HBVac T:92 T:0 ?
图3 不同干预措施效果的直接Meta分析
图4 四种预防HBV母婴传播干预措施的网络Meta分析
图5 四种干预措施降低HBV母婴传播效果的累积排序概率图
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