以产妇人群为基础的免疫预防乙型肝炎病毒母婴传播的现实世界效果

Real-world efficacy of immunoprophylaxis against mother-to-infant transmission of hepatitis B virus based on puerperant population

目的评估我国免费使用乙型肝炎免疫球蛋白(hepatitis B immunoglobulin, HBIG)和乙型肝炎疫苗在现实世界中预防乙型肝炎病毒(hepatitis B virus, HBV)母婴传播的效果。方法以江苏省如皋市2011年7月1日至2016年6月30日所有61 790例活产产妇为研究对象,回顾性分析乙型肝炎表面抗原(hepatitis B surface antigen, HBsAg)筛查率、阳性率和HBsAg阳性母亲的新生儿联合免疫预防、婴幼儿在7月龄后随访乙型肝炎感染状况。2018年4月再次随访HBsAg阳性婴幼儿及其母亲的乙型肝炎指标。采用Fisher精确概率法及趋势χ2检验分析组间和不同年份各指标的差异。结果产妇HBsAg筛查率为100.0%(61 790/61 790),其中产前筛查率为98.6%(60 937/61 790),呈逐年上升趋势(χ2趋势=750.908,P<0.001)。共有3 397例(5.5%)产妇HBsAg阳性,阳性率逐年下降(χ2趋势=32.667,P<0.001)。共随访759例HBsAg阳性母亲及其778例子女,其中男童399例(51.3%),女童379例(48.7%);初次随访月龄平均为(13.7±6.9)个月。751例(96.5%)子女确定接受正规免疫预防,25例(3.2%)可能接受正规免疫预防,2例(0.3%)未正规预防。共14例(1.8%)婴幼儿HBsAg阳性,均出生于乙型肝炎e抗原(hepatitis B e antigen, HBeAg)阳性母亲。538例出生于HBeAg阴性母亲的婴幼儿均未感染。2013年及以后出生的子女,母婴传播率低于2011年和2012年出生的婴幼儿(χ2趋势=13.352,P=0.000 3)。2018年4月对11例HBsAg阳性儿童及其母亲间隔4~5年再次随访,除1例母亲发生自发HBeAg血清学转换外,余10例母亲HBV DNA水平为(7.34~28.2)×107 IU/ml;11例感染儿童中,1例发生HBeAg血清学转换。HBV S基因分子进化树分析显示11对母子感染的病毒均为C基因型。结论自新生儿免费使用HBIG和乙型肝炎疫苗后,如皋市在预防HBV母婴传播的现实世界中,HBV母婴传播率进一步下降,与报道的临床研究传播率相似,说明该地区的免疫预防取得了良好的效果。

Objective To assess the efficacy of immunoprophylaxis against mother-to-infant transmission of hepatitis B virus (HBV) in a real-world setting since the implementation of charge-free hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in China. Methods The screening rate and the prevalence of hepatitis B surface antigen (HBsAg) in 61 790 puerperants, and the administration of combined immunoprophylaxis in infants of HBsAg-positive mothers in Rugao City of Jiangsu Province from July 1, 2011 to June 30, 2016 were retrospectively analyzed. HBV infection status of infants born to HBV infected mothers was followed up after 7 months of age. HBsAg-positive infants and their mothers were followed up again for HBV markers in April 2018. Fisher's exact test and Cochran-Armitage trend test were used to statistically analyze the differences between groups and various years, respectively. Results All 61 790 puerperants were screened for HBsAg and the prenatal screen rate was 98.6%(60 937/61 790) with an increasing trend over time (χ2trend=750.908, P<0.001). HBsAg-positive puerperants accounted for 5.5%(3 397/61 790) with a decreasing trend over time (χ2trend=32.667, P<0.001). In total, 778 offspring (399 boys and 379 girls) of 759 HBsAg-positive mothers were followed up at (13.7±6.9) months of age, among which 751 (96.5%) were administered and 25 (3.2%) were probably administered standard combined immunoprophylaxis after birth, and the rest two (0.3%) were not. Fourteen infants (1.8%) were HBsAg positive and all born to mothers with positive hepatitis B e antigen (HBeAg). None of the 538 infants born to HBeAg-negative mothers was HBsAg-positive. HBsAg-positive rate in infants born since 2013 was lower than those in 2011 and 2012 (χ2trend=13.352, P=0.000 3). Eleven HBsAg-positive mothers and their children were followed up again 4–5 years later in April 2018. HBV DNA levels of all mothers were within the range of (7.34–28.2)×107 IU/ml except one case of spontaneous HBeAg seroconversion. One out of the 11 infected children also had HBeAg seroconversion. Phylogenetic analysis of HBV S gene showed that the 11 pairs of mothers and children were all infected with HBV of genotype C. Conclusions The implementation of charge-free HBIG and hepatitis B vaccine for newborns achieves fruitful results in Rugao city as the mother-to-infant transmission of HBV in the real-world had been further reduced to a similar level reported in literature survey.