母亲乙型肝炎表面抗原基因变异与新生儿免疫预防失败无关

A study of neonatal immunoprophylaxis failure not correlated with mutations of maternal hepatitis B virus S gene

目的探讨乙型肝炎病毒(hepatitis B virus,HBV)感染母亲HBV S基因变异与新生儿免疫预防失败的关系。方法纳入乙型肝炎(乙肝)表面抗原(hepatitis B surface antigen, HBsAg)阳性、经PCR扩增HBV S基因并测序成功的660例产妇以及其随访的子女673例。根据母亲HBV S基因a决定簇和主要亲水区(major hydrophilic region,MHR)有无变异,将母亲分为变异组和未变异组,比较两组新生儿免疫预防失败率。同时比较新生儿免疫预防成功组和预防失败组母亲的HBV S基因变异率。结果 673例子女中,14例(2.1%)发生慢性感染,均为乙肝e抗原(hepatitis B e antigen, HBeAg)阳性母亲的子女(14/273,5.1%),400例HBeAg阴性母亲的子女感染率为0(P<0.001)。660例母亲中,S基因a决定簇氨基酸发生变异166例,不包含a决定簇(124~147位氨基酸)的MHR氨基酸发生变异141例。HBeAg阴性母亲a决定簇变异率(31.8%)高于HBeAg阳性母亲(15.6%)(P<0.001)。a决定簇和MHR变异率在HBV感染预防成功组(分别为25.3%和21.5%)和预防失败组(分别为16.7%和16.7%)母亲差异无统计学意义(P值分别为0.728和0.964)。在270例HBeAg阳性母亲中,HBV感染预防成功组和预防失败组的a决定簇(15.5%和16.7%,P=1.000)以及MHR变异率(10.1%和16.7%,P=0.804)差异无统计学意义。在所有母亲中,a决定簇变异和未变异的母亲,其子女感染率分别为1.2%和2.4%(P=0.535),MHR变异和未变异的母亲其子女感染率分别为1.4%和2.3%(P=0.715)。在HBeAg阳性母亲中,a决定簇变异与未变异的母亲其子女感染率分别为4.8%和5.2%(P=1.000),MHR变异和未变异的母亲其子女感染率分别为7.1%和4.9%(P=0.954)。结论本研究结果表明,新生儿免疫预防失败与母亲HBV S基因变异无明显关系,而是与HBeAg阳性母亲的高病毒载量有关。

Objective To study the relationship between S gene mutations of maternal hepatitis B virus(HBV)and the failure of neonatal immunoprophylaxis against hepatitis B.Methods A total of 660 HBsAg-positive mothers whose HBV S gene were successfully sequenced,and the immunoprophylaxis resuts of their 673 babies were analyzed.The rates of immunoprophylaxis failure were compared between the offsprings born to mothers with and without mutations in the a determinant(amino acids 124-147)of S gene and the major hydrophilic region(MHR)outside the a determinant(MHRa-).The prevalence of S gene mutant in mothers whose offsprings were protected against HBV was compared with that infected with HBV.Results Of all of the 673 children,14(2.1%)were infected with HBV.All infected children were among those 273(5.1%)children with HBeAg-positive mothers,while no infections were found in the remaining 400 children with HBeAg-negative mothers(P<0.001).Mutations in the adeterminant were observed in 166 of the 660 mothers.In addition,141 mothers carried HBV with mutations in MHRa-.The mutant prevalence in the adeterminant was higher in HBeAg-negative mothers than that in HBeAg-positive mothers(31.8%vs 15.6%,P<0.001).Overall,the mutant prevalence in the adeterminant and MHRa-in the successful immunoprophylaxis group was 25.3%and 21.5%,respectively,while 16.7%and 16.7%,respectively in the immunoprophylaxis failure group(P=0.728 and 0.964,respectively).Among the 270 HBeAg-positive mothers,the immunoprophylaxis success and failure groups showed similar mutant prevalence in the adeterminant(15.5%vs 16.7%,P=1.000)and in the MHRa-(10.1%and 16.7%,P=0.804).Overall,the immunoprophylaxis failure occurred in 1.2%and 2.4%children born to mothers with and without mutations in the adeterminant,respectively(P=0.535),and in 1.4%and 2.3%children born to mothers with and without mutations in the MHRa-,respectively(P=0.715).Among 270 HBeAg-positive mothers,immunoprophylaxis failure occurred at 4.8%and 5.2%children born to mothers with and without the amutations,respectively(P=1.000),and 7.1%and 4.9%children born to mothers with and without in MHRa-mutations,respectively(P=0.954).Conclusions No significant correlation was found between the failure of neonatal immunoprophylaxis against HBV and the mutations of maternal HBV S gene,but associated with maternal positive HBeAg and high viral loads.