慢性肝病患者拉米夫定耐药毒株突变模式特征分析  

Analysis of Lamivudine-resistant variants mutation patterns in patients with chronic hepatitis disease

作　　者：欧阳雅博[1] 李庆[1] 魏飞力[1] 张玉林[1] 黄雁翔[1] 宋晨朝[1] 郭向华[1] 谢放[1] 王珊珊[1] 陈德喜[1] 

机构地区：[1]首都医科大学附属北京佑安医院北京市肝病研究所,北京100069

出　　处：《中华实验和临床病毒学杂志》2017年第1期31-34,共4页Chinese Journal of Experimental and Clinical Virology

基　　金：国家自然科学基金（81361120401）;首都卫生发展科研专项（2014-1-1151）;北京市优秀人才培养资助青年骨千个人项目（2015000021469G183）;佑安肝病艾滋病基金资助中青年人才孵育项目（YNKT20160015）

摘　　要：目的 探讨拉米夫定（LAM）耐药毒株突变模式及HBV S基因相关变异在不同疾病进展慢性肝病患者中的特征.方法 收集LAM耐药慢性肝病患者的血液标本,获得相应的HBV RT基因核苷酸序列,分析耐药突变位点、药物耐受和耐药相关HBV S基因变异特点及组间差异.结果 本研究纳入慢性乙型肝炎（CHB）患者47例,乙肝肝硬化（LC）和乙肝相关肝细胞癌（HCC）患者16例.M204I单点突变与L180M＋M204I/V为LAM耐药的慢性肝病患者最常见突变形式（35/63,55.56％）.LC/HCC组对三种以上核苷（酸）类似物同时耐药人数高于CHB组（62.50％ vs 34.04％,P =0.046）.LC/HCC组在HBV-S区检测到与免疫逃逸相关的HBsAg突变位点数多于CHB组（62.50％ vs 31.91％,P=0.031）,I126T/V与G145A（LCC/HCC,60％）、I126S/T与S117T（CHB,46.67％）为HBsAg逃逸突变的最常见形式.两组患者均检测到RT区变异伴随HBsAg终止密码子的突变（rtA181T/sW172＊和rtM204I/sW196＊）.结论 不同疾病进展慢性肝病患者LAM耐药毒株突变及相关HBV S基因变异特征存在差异,LC/HCC患者多重耐药和免疫逃逸毒株比例高于CHB患者.Objective To investigate the genetic characteristics of Lamivudine-resistant mutation patterns and HBV S gene mutants in patients with chronic hepatitis disease of different disease progression.Methods Blood samples of LAM-resistant patients with chronic hepatitis disease were collected.HBV RT gene nucleotide sequences were obtained,and then differences in drug-resistant mutation patterns,drug susceptibility and HBV S gene mutants characteristics between the two groups were analyzed.Results Forty-seven chronic hepatitis B （CHB） patients and 16 HBV-related liver cirrhosis （LC）/HBV-related hepatocellular carcinoma （HCC） patients were included in this study.M204I single point mutation and L180M ＋ M204I/V were the most common pattern during patients with chronic hepatitis disease （35/63,55.56%）.The numbers of resistant to three nucleos （t） ide analogues in LC/HCC group was higher than CHB group＇s （62.50% vs 34.04%,P =0.046）.In HBV S gene,more immune associated HBsAg-escape mutations were detected in LC/HCC group than that in CHB group （62.50% vs 31.91%,P =0.031）.I126T/V and G145A （for LCC/HCC group,60%）,I126S/T and S117T （for CHB group,46.67%） were showed as the most common form for HBsAg escape mutations in the two groups.The two groups both detected RT mutations concomitantly with stop codon mutations in S gene （rtA181T/sW172 ＊ and rtM204I/ sW196 ＊）.Conclusions Different characteristics in Lamivudine-resistant mutations and associated HBV S gene mutants were found in patients with chronic hepatitis disease of different disease progression,and LC/ HCC patients exhibit more multi-drug resistant variants and immune associated HBsAg-escape mutants than CHB patients.

关 键 词：肝炎病毒  乙型 慢性肝病 拉米夫定 耐药突变 S基因突变 

分 类 号：R512.62[医药卫生—内科学]