拉米夫定停药后出现肝衰竭患者hbv基因型及基因变异

hbv genotypes and gene mutations in patients with liver failure after withdrawal of lamivudine

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.abstract：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.