拉米夫定耐药患者乙型肝炎病毒的基因突变  

Analysis of hepatitis B virus gene mutation pattern of 444 cases of lamivudine-resistant patients

作　　者：郑瑞英[1] 万谟彬[1] 李成忠[1] 陈志辉[1] 张迁[1] 陈姬秀[1] 张斌[1] 薛建亚[1] 梁雪松[1] 

机构地区：[1]第二军医大学长海医院感染科,上海200433

出　　处：《中华传染病杂志》2007年第7期412-416,共5页Chinese Journal of Infectious Diseases

摘　　要：目的了解在拉米夫定治疗慢性乙型肝炎的过程中出现拉米夫定耐药患者的HBV YMDD突变模式及其特性。方法回顾性分析444例在拉米夫定治疗过程中出现耐药突变的慢性乙型肝炎病例,用基因芯片法检测YMDD突变类型.并分析不同突变类型的特点。结果444例拉米夫定耐药患者的YMDD突变类型分别为:YVDD突变185例,其中合并L180M突变94例;YIDD突变216例,其中合并L180M突变34例;YVDD突变+YIDD突变43例,其中合并L180M突变18例。相对于YVDD突变株,YIDD突变株检出率高,较易出现于相对年长患者,发生突变时间晚,病毒复制水平高,肝炎复发程度相对较重。合并L180M突变较单纯YMDD突变发生早,病毒复制水平高。结论拉米夫定耐药的YMDD突变模式主要为点突变和联合突变两种,点突变以YIDD突变为主,联合突变以YVDD突变合并L180M突变为主,YMDD突变模式不同者的临床表现不同,YMDD突变模式可能与预后及治疗的应答相关。Objeetive To study the patterns and characteristics of YMDD motif mutation in hepatitis B virus（HBV） polymerase gene in patients with drug-resistance during lamivudine treatment. Methods Four hundreds and forty-four patients with chronic hepatitis B who exhibited drugresistant mutation during lamivudine treatment were retrospectively analyzed. YMDD motif mutation types were determined by gene chips, and the characteristics of different types of YMDD motif mutation were analyzed. Results There were 185 cases of YVDD mutation, 216 cases of YIDD mutation and 43 cases of YVDD ＋ YIDD mutation among 444 patients. Rate of combination of an additional L180M mutationof them were 50.81%（94 cases）, 15.74%（34 cases） and 41.86%（18 cases）, respectively. Compared with YVDD mutants, the detection rate of YIDD mutants were higher and it occurred in older patients, mutated later, its serum HBV DNA level was higher, and the flare of hepatitis was more severe. YMDD mutation with L180M emerged earlier and had higher levels of serum HBV DNA than YMDD mutation only. Conclusions Point mutation and combined mutation are dominant in YMDD mutation patterns. YIDD mutation is dominant in point mutation and YVDD combined with L180M mutation is dominant in combination mutation. The clinical manifestations are different in patients with different types of YMDD mutation. The type of YMDD motif mutants can affect the clinical prognosis and therapeutic effects.

关 键 词：肝炎病毒 乙型 YMDD突变 拉米夫定 药物耐受性 

分 类 号：R512.62[医药卫生—内科学]