医院就诊人群HBsAg与抗HBs双阳性HBV感染者的流行病学与分子病毒学特征

摘要

Objective To investigate the epidemiological and molecular virological characteristics in HBV-infected patients with copositive HBsAg and anti-HBs.Methods HBV serological markers were analyzed in 52 070 specimens.The epidemiological characteristics of HBsAg and anti-HBs simultaneously positive patients (the experimental group) and HBsAg positive and auti-HBs negative patients (the control group) were compared.The S protein of HBV coding region was amplified by semi-nested PCR and sequenced.The statistical differences between the two groups were compared in different gene regions,genotypes and different clinical diagnosis.Results HBsAg was positive in 20.40％ (10 621/52 070) of all specimens.In the patients with positive HBsAg,2.48％ (263/10 621) was positive anti-HBs.The prevalence of co-positive HBsAg and auti-HBs was higher in aged 0 to 9 years and greater than or equal to 80 years than that in other age,and the prevalence of positive HBsAg and negative anti-HBs was completely opposite.The mutation rate of S protein in the experimental group was significantly higher than that in the control group (1.52％ vs 0.81％,P ＜0.01) with the mutation in the major hydrophilic region (MHR) (1.68％ vs 0.57％,P ＜0.01).The mutation rates of S protein of HBV carriers,chronic hepatitis B (CHB) patients and patients with liver cirrhosis (LC) in the experimental group were significantly higher than those in the control group (1.47％ vs 0.65％,1.28％ vs 0.84％,2.21％ vs 0.44％,P ＜0.05,respectively),except for the patients with hepatocellular carcinoma (HCC) (1.97％ vs 2.21％,P ＞ 0.05).Conclusion Co-positive HBsAg and anti-HBs in HBV-infected patients was more common in HBsAg positive patients aged 0 to 9 years and greater than or equal to 80 years than the others.Coexistence of HBsAg and anti-HBs in HBV-infected patients may relate to immune escape caused by mutation of S protein (mainly MHR).The mutation rates of S protein in the two groups of patients,co-positive HBsAg and anti-HBs and the positive HBsAg combined with negative anti-HBs,were associated with the stage of liver disease.%目的 探讨乙型肝炎病毒表面抗原(HBsAg)和抗HBsAg抗体(抗HBs)同时阳性的HBV感染者的流行病学及分子病毒学特征.方法 分析52 070例医院就诊人群HBV血清学标志物检测结果,以HBsAg和抗HBs双阳性患者为实验组,HBsAg阳性、抗HBs阴性患者为对照组,比较2组患者的流行病学特征.半巢氏PCR扩增2组患者HBV S蛋白编码区并测序,比较2组间在不同基因区、基因型及临床诊断时的统计学差异.结果 医院检测人群HBsAg阳性率为20.40％ (10 621/52 070),其中HBsAg、抗HBs双阳性率为2.48％ (263/10 621).HBsAg、抗HBs双阳性在0～9岁和≥80岁人群流行率较高,而HBsAg阳性、抗HBs阴性则相反.实验组S蛋白氨基酸突变率显著高于对照组(1.52％ vs 0.81％,P＜0.01),差异主要存在于主要亲水区(MHR)(1.68％vs0.57％,P＜0.01).实验组中除肝癌(HCC)患者外(1.97％ vs 2.21％,P＞0.05),乙肝携带者、慢性乙型肝炎(CHB)患者和肝硬化(LC)患者的S蛋白突变率均显著高于对照组同疾病患者(分别为1.47％ vs 0.65％,1.28％ vs0.84％,2.21％ vs 0.44％,P均＜0.05).结论 HBsAg、抗HBs双阳性以0～9岁和≥80岁HBsAg阳性人群更多见.HBV感染者血清HBsAg和抗HBs共存可能与S蛋白(主要为MHR)的突变造成的免疫逃逸有关.HBsAg、抗HBs双阳性和HBsAg阳性、抗HBs阴性患者之间S蛋白的突变率差异与患者肝脏疾病所处的阶段有关.