核苷类似物抗病毒治疗失败的慢性乙型肝炎患者基因型耐药分析  

Evoluation of patients with chronic hepatitis B resistant to nucleoside analog therapy

作　　者：刘海霞[1] 李娟[1] 朱跃科[1] 王金环[1] 冯岩梅[1] 于红卫[1] 孟庆华[1] 

机构地区：[1]首都医科大学附属北京佑安医院重症肝病科,北京100069

出　　处：《临床荟萃》2011年第16期1385-1387,共3页Clinical Focus

摘　　要：目的了解慢性乙型肝炎患者服用核苷类似物抗病毒治疗失败后,病毒基因型耐药变异情况,为选择新抗病毒治疗方案提供参考依据。方法分别选取服用拉米夫定和阿德福韦酯抗病毒治疗失败的患者作为研究对象,用巢式聚合酶链反应(ntPCR)方法扩增目的基因片段,并对其进行序列测定及分析,检测与病毒耐药相关的突变点位。结果 20例患者出现与耐药相关的突变位点。11例拉米夫定治疗患者,发生rtM204V/I突变10例(90.9%),出现rtL180M/I/L位点突变5例(45.5%),出现rtA181V位点突变1例(9.0%),出现M204I单位点耐药突变5例(45.5%),出现包含180和204位点的多个位点联合突变6例(54.5%)。9例阿德福韦酯治疗患者出现rtA181T或rtN236T单位点突变各4例(44.4%),出现rtA181T+rtN236T联合突变1例(11.1%)。结论乙型肝炎病毒(HBV)耐药变异株的出现是抗病毒失败的主要原因,目前临床上服用拉米夫定和阿德福韦酯抗病毒治疗的患者较多,拉米夫定治疗的患者也可以出现rtA181V位点突变,该位点突变出现可以发生二者的交叉耐药。防止多药耐药的发生具有重要的意义,建议抗病毒治疗失败后参考基因型耐药检测结果更换药物。Objective To evoluate genotypic drug resistance prevalence in treatment failure patients with chronic hepatitis（CHB）.Methods Peripheral venous blood samples were collected from the patients who failed antiviral therapy,and were amplified by nested PCR;then the amplified fragments were sequenced and analyzed.Results 20 samples which were successfully amplified came from 11 lamivudine（LAM） resistant patients and 9 adeforvir（ADV） resistant patients.M204V/I and L180M/I/L were the most common mutations seen in the 10 patients and 5 patients separately among the LAM resistant patients.5 cases（45.5%） of LAM resistant isolate samples were found rtM204I single mutations.The other 6 cases（54.5%） sample included 180 and 204 sit or the other sit mutations.One case（9.0%） contained 181 mutation which means cross resistance to ADV.According to the genotype analysis,the ADV resistance mutations rtA181V/T,rtN236T,and both together,were observed in 4 cases（44.4%）,4 cases（44.4%）,and 1 case（11.1%）,respectively.Conclusion Antiviral drug resistance now poses a major problem in the management of patients with CHB.Among nucleoside analogs,LAM and ADV have been most widely used in treatment of CHB.Substitutions at rtA181V have also been found after virologic breakthrough during LAM therapy in patients who were never treated with ADV;these mutations confer cross-resistance to both LAM and ADV.These results emphasize the importance in preventing the development of multidrug-resistant HBV.Our finding suggested that rescue antiviral therapy regimens are needed based on the genotype drug resistance test findings.

关 键 词：肝炎 乙型 慢性 拉米夫定 阿德福韦酯 突变 基因 MDR 

分 类 号：R512.6[医药卫生—内科学]