儿童乙肝表面抗原和表面抗体共阳性者病毒preS/S基因变异特征

A study on preS/S variants of hepatitis B virus in children with coexisting HBsAg and HBsAb

目的 探讨儿童中乙肝表面抗原和抗体共阳性乙型肝炎病毒(HBV)感染者preS/S基因变异特征。方法 收集14岁以下儿童中乙肝表面抗原和抗体共阳性HBV感染者10例为共阳性组,以同期收集的儿童乙肝表面抗原单阳性22例为单阳性组,检测乙肝血清免疫学和肝功能标志物,应用荧光PCR检测血清HBV-DNA水平,对核酸检测阳性样本的病毒preS/S基因进行扩增,产物进行直接测序,分析2组间病毒preS/S区变异及临床特征差异。结果 共阳性组中以HBeAg阴性占大多数,且共阳性组儿童HBV-DNA水平低于单阳性组(P<0.05),但2组间基因型分布和肝功能指标差异无统计学意义(P>0.05)。通过与GenBank中HBV参考序列比较显示,共阳性组中主要亲水区(major hydrophilic region, MHR)和第二环内氨基酸变异率高于单阳性组,且共阳性组中检测出preS2缺失突变。结论 乙肝表面抗原和抗体共阳性儿童HBV感染者病毒呈低水平复制,preS/S变异可能与儿童共阳性发生有关。

Objective This paper aims to investigate the variation of preS/S gene in children with coexisting hepatitis B surface antigen and antibody.Methods Ten cases with coexisting hepatitis B surface antigen(HBsAg)and antibody(HBsAb)under 14 years old were selected as the experimental group.22 children with single HBsAg positive were selected as control group.All cases underwent the detection of serum immunological and liver function markers.The serum HBV-DNA level was detected by fluorescent PCR,and the preS/S gene was amplified.The products were directly sequenced to analyze the variations of preS/S region and the difference of clinical characteristics between the two groups.Results HBeAg negative was the majority of the experimental group,while the HBV-DNA level of the experimental group was lower than that of the control group(P<0.05).There was no statistical significance on the difference in genotype distribution and liver function indexes between the two groups(P>0.05).A comparison with the HBV reference sequence in GenBank showed that the amino acid variation rate in the major hydrophilic region(MHR)and the second loop was higher in the experiment group than that in the control group,and preS2 deletion mutation was detected in the experiment group.Conclusion HBV in children with coexisting hepatitis B surface antigen and antibody showed low level replication,and preS/S mutation may be associated with coexisting of HBsAg and HBsAb.