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

Epidemiological and molecular virological characteristics of HBV infected patients of hospital with simultaneously positive HBsAg and anti-HBs

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%vs 0.57%,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。

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 anti-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 anti-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.