HBV基因型和S基因序列特点与慢性乙型肝炎患者HBsAg/抗-HBs共存关系

目的探讨HBV基因型及S基因序列特点与慢性乙型肝炎（CHB）患者HBsAg和抗-HBs共存的内在相关性以及HBsAg＋/抗-HBs＋的发生机制及意义。方法共收集49例HBsAg＋/抗-HBs＋CHB患者的血清HBVDNA样本,采用PCR-RFLP及测序法鉴定其基因型,并与267例HBsAg＋/抗-HBs-CHB患者的HBV基因型分布进行比较。对6例HBsAg＋/抗-HBs＋CHB患者（Ⅰ组）的HBVS基因进行克隆测序,并与HBsAg＋/抗-HBs-CHB患者（Ⅱ组）进行对比,分析变异种类及频率等的差异。结果 HBsAg＋/抗-HBs＋CHB患者HBV基因型B、C及B/C混合感染的构成比分别为63.3%（31/49）、26.5%（13/49）、10.2%（5/49）,而对照组上述构成比分别为52.8%（141/267）、46.1%（123/267）、1.1%（3/267）,两组构成比差异有统计学意义（P〈0.01）。Ⅰ组HBsAg各区段,特别是主要亲水区（MHR）的变异位点明显多于Ⅱ组;发现了若干新变异、少见的W196和C69终止突变,1例患者检测到G145R变异。某些患者HBsAgMHR-2（包含a决定簇）并未发现变异。结论 HBV基因型的差异及HBsAg变异增多可能是部分CHB患者出现HBsAg＋/抗-HBs＋的原因之一;基因型B或B/C混合感染相对更易出现HBsAg＋/抗-HBs＋。HBsAg变异增多是CHB患者出现HBsAg＋/抗-HBs＋的重要机制之一。某些患者HBsAgMHR-2并无变异,提示HBsAg/抗-HBs共存还存在其他机制。

The correlations between HBV genotypes and HBsAg mutaion and coexistence of HBsAg/anti-HBs in patients with chronic hepatitis B

Objective To investigate the correlations between HBV genotypes and HBsAg mutaion and coexistence of HBsAg/anti-HBs（HBsAg＋/anti-HBs＋）in patients with chronic hepatitis B（CHB）,and to further reveal the mechanisms and significance of HBsAg＋/anti-HBs＋ in CHB patients.Methods HBV genotypes of 49 CHB patients with HBsAg＋/anti-HBs＋ and 267 CHB patients with HBsAg＋/anti-HBs-were determined by PCR-RFLP and sequencing HBV S gene from 6 HBsAg＋/anti-HBs＋ CHB patients（groupⅠ）were cloned and sequenced.HBs mutations and their frequencies were analysed.Results The ratios of HBV genotypes B,C and B/C were 63.3%（31/49）,26.5%（13/49）and 10.2%（5/49）in groupⅠ,yet 52.8%（141/267）,46.1%（123/267）and 1.1%（3/267）in groupⅡ,respectively（P0.01）.No other HBV genotypes were found in all of the patients.HBsAg mutations,especially in the major hydrophilic regions（MHR）,were more often found in groupⅠthan those in groupⅡ.Several new mutations were reported in groupⅠfor the first time,including the rare stop mutations of W196 and C69;and the classic mutation G145R was seen in one of the five clones in one patient.The amounts,sites and kinds of mutations were greatly different in the two goups.No mutations was found in HBsAg MHR-2 in some of the HBsAg＋/anti-HBs ＋ CHB patients.Conclusion HBsAg＋/anti-HBs＋may exist in CHB patients infected with HBV genotype B,C or mixture of B/C,especially in patients infected with genotype B or mixture of B/C.The high frequency of mutations and some of the newly found mutations in HBsAg may contribute to the development of HBsAg＋/anti-HBs＋ in CHB patients.Other mechanisms should be involved because some of the HBsAg＋/anti-HBs＋CHB patients have no mutations in HBsAg MHR-2.