学龄前儿童乙型肝炎疫苗无应答者HBV感染风险的前瞻性队列研究

A prospective cohort study on the risk of HBV infection in preschool children without immune response to hepatitis B vaccine

目的评估学龄前儿童乙肝疫苗无应答者未来感染乙肝病毒(hepatitis B virus,HBV)的风险。方法采用前瞻性队列研究的方法,选取南宁市江南区64家幼儿园内、已经按照0、1、6程序全程接种了三针乙肝疫苗的2～5岁儿童,在2015年3～5月期间抽血检测乙肝病毒表面抗原(hepatitis B surface antigen,HBs Ag)和乙肝病毒表面抗体(hepatitis B surface antibody,抗-HBs),HBs Ag阴性儿童为本次研究对象。根据儿童抗-HBs是否阳性,分成暴露组(抗-HBs阴性)和对照组(抗-HBs阳性)。研究开始于2015年6月1日,结束于2016年6月1日,在2016年6月1～30日对儿童进行随访检测血清HBs Ag阳性率,比较两个组的HBs Ag阳性率。结果纳入队列的无应答组人数1 907名,排除随访期间再次接种乙肝疫苗的83人,该队列人数实际为1 824,研究结束时失访151人,实际随访到的人数是1 673人,期间共有5名小孩HBs Ag转成阳性,感染率为0. 30%(5/1673);纳入队列的应答组人数2 054名,研究结束时失访140人,随访到人数为1914,他们均未检测出HBs Ag;研究结束时无应答组HBs Ag阳性率高于应答组(P=0. 023)。结论乙肝疫苗无应答者未来存在感染HBV的风险。

Objective To evaluate the risk of hepatitis B virus( HBV) infection among preschool children who were the non-responders to hepatitis B vaccine in future. Methods A prospective cohort study was conducted. Children aged 2 to 5 years were selected from 64 kindergartens. These children were inoculated three doses of hepatitis b vaccine at 0,1 and 6 months after birth. Hepatitis B surface antigen( HBs Ag) and Hepatitis B surface antibody( anti-HBs) were detected during the period from March to May2015. The children who were HBs Ag negative were enrolled in the study. The subjects were divided into exposure group( anti-HBs negative) and control group( anti-HBs positive). The follow-up began on June 1,2015 and ended on June 1,2016. Serum HBs Ag of children in the cohort was then collected and detected from June 1 to 30,2016. At the end of the study,the HBs Ag positive rates between two groups were compared. Results 83 children who received hepatitis B vaccine again during the follow-up period were excluded from 1 907 non-responders. The actual number in non-responders group was 1 824. 151 children were lost at the end of the study. The actual number of follow-up was 1 673 and 5 children were found to be positive for HBs Ag and the infection rate was 0. 30%( 5/1673). In the respondent goup,2 054 were enrolled and followed. Finally,140 children were lost and none of the remaining 1 914 people were HBs Ag positive at the end of the study. HBsAg positive rate was higher in the non-responder group than in the responder group( P = 0. 023). Conclusion There is a risk of HBV infection in the children who are non-responders to hepatitis B vaccine in future.