主动免疫在预防HBcAb阳性供肝儿童肝移植术后新发乙型肝炎病毒感染中的应用

Application of active immunization in the prevention of de novo hepatitis B virus infection after pediatric liver transplantation with HBcAb positive donor liver

目的 探讨主动免疫方式对接受乙型肝炎核心抗体（HBcAb）阳性供肝肝移植患儿术后新发乙型肝炎病毒（HBV）感染的预防作用.方法 回顾性分析2012年10月至2016年12月天津市第一中心医院87例接受HBcAb阳性供肝肝移植患儿及其供者的资料.所有患儿术前均注射乙型肝炎（乙肝）疫苗,使乙肝表面抗体（HBsAb）滴度〉1000 U/L;术中给予乙肝免疫球蛋白（HBIG）100 U/kg,使患儿迅速获得被动免疫以预防HBV感染;术后对HBsAb滴度〈200 U/L的患儿注射乙肝疫苗以加强免疫.术前及术后随访期间定期检测患儿的乙肝血清学标志物及肝功能,随访截至2017年4月.按患儿术后是否新发HBV感染分为两组,观察患儿移植术前及术后主动免疫方式对新发HBV感染的预防作用.结果 87例接受HBcAb阳性供肝肝移植的患儿中,9例（10.3％）新发HBV感染,术后发生感染的中位时间为16（10,25）个月.9例新发HBV感染患儿中7例术前HBsAb滴度〈1000 U/L,所占比例明显大于无新发HBV感染者〔77.8％（7/9）比37.2％（29/78）,P〈0.05〕.术后78例无新发HBV感染患儿中,62例成功接种乙肝疫苗,1例接种乙肝疫苗后HBsAb滴度仍然〈200 U/L,15例未接种乙肝疫苗者仅注射HBIG预防.新发乙肝患儿术后HBsAb滴度均〈200 U/L,所占比例明显大于无新发HBV感染者〔100.0％（9/9）比20.5％（16/78）,P〈0.01〕.结论 采取预防性治疗方法,通过建立主动免疫的方式,可以有效预防接受HbcAb阳性供肝的肝移植儿童受者新发HBV感染.

Objective To investigate the effect of active immunization on prevention of post-transplantation de novo hepatitis B virus （HBV） infection in patients receiving liver grafts from hepatitis B core antibody （HBcAb） positive donors.Methods A retrospective analysis was conducted. Eighty-seven children undergoing liver transplantation from HBcAb positive donors admitted to Tianjin First Center Hospital from October 2012 to December 2016 were enrolled, and the data of donors and recipients were collected. The hepatitis B vaccine was given before operation for hepatitis B surface antibody （HBsAb） 〉1000 U/L; hepatitis B immunoglobulin （HBIG） 100 U/kg was given during the operation, in order to prevent children from HBV infected by obtaining passive immunity quickly, children with HBsAb〈 200 U/L after operation were injected with hepatitis B vaccine for booster immunization. HBV markers and liver function of recipients were determined before liver transplantation and during the follow-up, which up to April 2017. According to the children got de novo HBV infection after operation or not, the preventive effect of active immunization before and after transplantation operation on HBV infection was analyzed and compared.Results In 87 children who received HBcAb positive donor livers, 9 （10.3%） developed de novo HBV infection, which occurred in 16 （10, 25） months after liver transplantation. Among the 9 children with HBV infection, 7 children had HBsAb 〈 1000 U/L before the operation, the ratio was statistically increased as compared with the children without HBV infection [77.8% （7/9） vs. 37.2% （29/78）,P 〈 0.05]. After the transplantation, 62 children of 78 without HBV infection showed a good response to hepatitis B vaccination, 1 child after inoculation of hepatitis B vaccine, the titer of HBsAb was still less than 200 U/L, 15 children without administration of hepatitis B vaccine, only with HBIG injection for prevention. The HBsAb of children with de nove HBV infection were less than 200 U/L after operation, the ratio was significantly increased as compared with children without HBV infection [100.0% （9/9） vs. 20.5% （16/78）,P 〈 0.01].Conclusions The establishment of active immunization method can effectively prevent children with de novo HBV infection occurred inpediatric recipients from HBcAb positive donors with preventive treatment.