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目的 研究拉米夫定治疗慢性乙型肝炎(CHB)停药后复发及出现肝衰竭患者的HBV基因型和基因变异的特点.方法 将拉米夫定治疗CHB停药后复发的患者按临床诊断分为肝衰竭组(12例)和慢性肝炎组(12例),采集患者临床资料和血清,从血清中提取HBV DNA,用PCR扩增,克隆后进行HBV测序和基因分型.结果 肝衰竭组中有6例成功完成测序,其中B、C基因型各3例;慢性肝炎组中有9例成功完成测序,其中B、C基因型分别是2例和7例.HBV序列与野生株比较,均出现能够引起包括编码S、P、C、X蛋白氨基酸改变的多个位点的变异.在同一基因型中,各病毒株之间的变异具有较高的一致性,P区出现变异的机会最多.拉米夫定停药后出现肝衰竭患者的HBV序列中可检测到位于BCP区、P区内高度保守序列的变异.结论 拉米夫定停药后出现肝衰竭的患者HBV基因B型和基因C型各占一半,出现位于BCP区和P区内高度保守序列变异的患者拉米夫定停药后更易出现肝衰竭.

Objective To investigate HBV genotypes and gene mutations in chrenic hepatitis B (CHB) patients with liver failure after lamivudine withdrawal. Methods Twenty four patients with relapsing CHB after lamivudine withdrawal were divided into liver failure group ( n = 12 ) and chronic hepatitis group ( n = 12 ). HBV DNA from these patients was amplified by PCR. The PCR products were cloned into PGEM-T vector and HBV DNA sequences were analyzed. Results In liver failure group, there were 6 sequences detected, in which 3 were of genotype B and 3 were of genotype C. In chronic hepatitis group, there were 9 sequences detected, in which 2 were of genotype B and 7 were of genotype C. Compared with the wild type HBV sequences, there were multiples mutations in S, P, C, X regions. Gene mutations in high conservative sequences of BCP and P regions were detected in liver failure patients after lamivudine withdrawal. Conclusions In HBV patients with liver failure after lamivudine withdrawal, half of them were of genotype B and the others were of genotype C. Some mutations in high conservative sequences of BCP and P regions may be related to the liver failure in these patients.