拉米夫定耐药后序贯治疗中HBV准种的演变  

Evolution of hepatitis B virus quasispecies during sequential therapy in patients with lamivudine-resistant hepatitis B virus infection

作　　者：吴珍萍[1] 韩涛[2] 高英堂[2] 李莹[2] 刘彤[2] 景丽[2] 刘磊[2] 杜智[2] 

机构地区：[1]天津医科大学三中心临床学院,天津市300170 [2]天津市第三中心医院天津市人工细胞重点实验室,天津市300170

出　　处：《世界华人消化杂志》2010年第8期779-785,共7页World Chinese Journal of Digestology

基　　金：国家重点基础研究发展规划(973计划)基金资助项目;No.2007CB512801;科技部科技重大专项基金资助项目;No.2008ZX10002-005;天津市科委重点攻关专项基金资助项目;No.05YFSZSF02500;天津市科委应用基础研究计划面上基金资助项目;No.06YFJMJC13100~~

摘　　要：目的:探讨拉米夫定(LAM)耐药后序贯治疗中HBV准种的演变特点.方法:收集7例拉米夫定耐药患者序贯治疗中的血清,对HBV聚合酶基因逆转录酶区进行PCR扩增克隆并测序,结合临床用药分析序列突变,探讨其演变特征.结果:患者1、4、5在序贯治疗中LAM耐药变异株一直存在,主要以M204I+L80I、M204I+L80I+L180M、M204V+L180M+G173L、M204V+L180M为主,所占比例在不断发生变化.患者2、3在序贯治疗中检测出野生株,但患者2在后续治疗中又选择出LAM耐药变异株.患者6在ADV联合ETV治疗时、患者7在单用ADV治疗时测时分别测出双重耐药株M204V+L180M+G173L+T184A和M204V+L180M+G173L+236D.结论:拉米夫定耐药后序贯治疗中原耐药突变不易消失,且容易在此基础上筛选出交叉耐药株或多重耐药株,他的出现影响序贯治疗的应答甚至导致序贯治疗的失败.AIM：To investigate the evolution characteristics of hepatitis B virus （HBV） quasispecies during sequential therapy in patients with lamivudineresistant HBV infection.METHODS：Serum samples were collected from seven patients with lamivudine-resistant HBV infection during sequential therapy.The reversetranscriptase （RT） region of the HBV polymerase gene was amplified,cloned and sequenced.Sequence mutations were analyzed to characterize the evolution of HBV quasispecies.RESULTS：Lamivudine-resistant strains were persistently present in the serum of patients 1,4 and 5.The main mutation patterns were M204I＋L80I,M204I＋L80I＋L180M,M204V＋ L180M ＋ G173 L,and M 20 V ＋ L180 M.T h e proportion of these mutant strains changed constantly.The wild-type strain was detected in patients 2 and 3.However,lamivudineresistant strains were detected in patient 2 during following therapy.Double-resistant mutant strains M204V＋L180M＋G173L＋T184A and M204V＋L180M＋G173L＋N236D were detected in patient 6,who underwent combination therapy with adefovir dipivoxil and lamivudine,and in patient 7,who underwent adefovir dipivoxil monotherapy.CONCLUSION：Lamivudine-resistant mutant strains in the serum of patients with HBV infection do not easily disappear during sequential therapy.Cross-resistant or multi-resistant strains of HBV quasispecies are often present during sequential therapy and affect the response to the therapy,thereby resulting in therapeutic failure.

关 键 词：拉米夫定 耐药 乙型肝炎病毒 准种 

分 类 号：R512.62[医药卫生—内科学]