乙型肝炎母婴传播阻断成功儿童乙型肝炎病毒突破性感染的特征

目的了解乙型肝炎(乙肝)母婴传播阻断成功儿童乙肝病毒(HBV)突破性感染及其影响因素。方法选取江苏省淮安市淮安区2009年9月-2011年1月乙肝表面抗原(HBsAg)阳性母亲所生儿童,且乙肝母婴传播阻断成功。阻断成功定义为儿童按国家免疫程序在完成出生时乙肝疫苗(HepB)和乙肝免疫球蛋白以及1、6月龄HepB接种后7-12月龄HBsAg阴性,HBV突破性感染定义为阻断成功儿童在12月龄后HBsAg阳性或24月龄后乙肝核心抗体(HBcAb)阳性。至2019年9月进行5次随访并检测HBV血清标志物,分析HBV突破性感染及其影响因素。结果本研究共纳入儿童390名,其中12名29-117月龄儿童发生HBV突破性感染,发生率为3.08%(12/390),均为乙肝核心抗体(HBcAb)阳性和HBsAg阴性。乙肝疫苗(HepB)初次免疫无、低、正常、高应答儿童HBV突破性感染率分别为25.00%、6.67%、2.61%、0.95%;母亲HBeAg阳性、阴性的儿童分别为9.76%、0.00%;母亲高、低HBV病毒载量的儿童分别为11.96%、0.34%。儿童HBV突破性感染发生密度为0.36/100人年;多因素Cox回归分析显示,HepB初次免疫低或无应答、母亲高病毒载量是儿童HBV突破性感染的危险因素(HR=5.91,95%CI:1.87-18.71;HR=45.81,95%CI:5.88-356.96)。结论乙肝母婴传播阻断成功儿童的HBV突破性感染发生率较低;母亲HBeAg阳性、母亲高HBV病毒载量、HepB初次免疫低或无应答的儿童更易发生突破性感染。

Characteristics of hepatitis B virus breakthrough infection among children with successful interruption of mother-to-child hepatitis B transmission

Objective To explore hepatitis B virus(HBV)breakthrough infection and its risk factors among children with successful interruption of mother-to-child transmission of hepatitis B.Methods We enrolled children born to hepatitis B surface antigen(HBsAg)-positive mothers between September 2009 and January 2011 in Huai’an district,Huai’an city,Jiangsu province,and who had successful interruption of mother-to-child transmission of hepatitis B virus.Successful interruption of transmission was defined as the infant being negative for HBsAg at 7 to 12 months of age,having received hepatitis B vaccine(HepB)and hepatitis B immune globulin at birth followed by HepB at 1 and 6 months,as recommended in the national immunization schedule.Breakthrough infection was defined as an infant with successful interruption of transmission who was positive for HBsAg after 12 months of age or positive for hepatitis B core antibody(HBcAb)after 24 months of age.We conducted 5 follow-up evaluations through September 2019,testing blood for HBV serum markers to determine the occurrence of HBV breakthrough infection and identifying risk factors for breakthrough.Results A total of 390 children were enrolled.HBV breakthrough infections occurred in 12 children,aged 29-117 months,for an overall breakthrough rate of 3.08%(12/390).All of the breakthrough cases were positive for HBcAb,and all were negative for HBsAg.HBV breakthrough infection rates were 25.00%,6.67%,2.61%,and0.95%for children with no,low,normal,and high responses to primary immunization with HepB.Breakthrough rates were 9.76%and 0.00%for children with positive and negative maternal HBeAg,respectively,and were 11.96%and0.34%for children with high and low maternal HBV viral loads.The incidence density of HBV breakthrough infection among children was 0.36 per 100 person-years.Multivariate Cox regression analysis showed that low or no response to primary immunization with HepB and high maternal viral load were risk factors for HBV breakthrough infection(HR=5.91,95%CI:1.87-18.71;HR=45.81,95%CI:5.88-356.96).Conclusions The incidence of HBV breakthrough infection was generally low among children with successful interruption of mother-to-child transmission of hepatitis B,but was high among children born to HBeAg positive mothers and mothers with high HBV viral loads,or who had low or no response to HepB primary immunization.