拉米夫定联合阿德福韦酯治疗慢性乙型肝炎应答不佳者基因型演变特点研究

Genotypes and evolution characteristics of three patients with poor response to initial treatment ofLamivudine and Adefovir dipivoxil for hepatitis

目的了解拉米夫定初始联合阿德福韦酯治疗慢性乙型肝炎应答不佳者基因型特点及其演变规律。方法应用克隆测序法检测3例患者（s1患者、s2患者、s3患者）拉米夫定初始联合阿德福韦酯治疗12个月以上病毒学应答不佳慢性乙型肝炎患者基线、治疗4周、12周、24周、48周、60周HBV基因型，每个时间点各随机挑取25个克隆进行鉴定并测序。结果3例初始联合拉米夫定和阿德福韦酯治疗慢型乙型肝炎应答不佳患者各时间点的总克隆数为398份，其中S1患者在基线时C基因型（8．3％）和B基因型（91．7％）共同表达，但B基因型占绝对优势（22／24）。治疗60周时c基因型占绝对优势（100％）。s2和s3患者在基线时仅表达B基因型，在治疗过程中，B基因型逐渐“漂移”为c基因型，治疗60周时，c基因型占绝对优势（s2中占75％，s3中占100％）。结论克隆测序可以更好的反应整体的基因型水平；在长期药物压力下HBV基因型从B基因型逐渐向C基因型演变，是导致拉米夫定初始联合阿德福韦酯治疗应答不佳的主要原因。

Objective To understand the genotype characteristics and its evolution of patients with poor response to initial combined treatment of Lamivudine and Adefovir dipivoxil for chronic hepatitis B. Methods We detected the HBV genotypes of three patients-S1, $2, $3, who with poor response to initial treatment of Lamivudine and Adefovir dipivoxil for chronic hepatitis B over 12 months by the application of cloning and sequencing method at the time point of baseline ,4 weeks after treatment, 12 weeks, 24 weeks, 48 weeks, 60 weeks. 25 clones were randomly selected to identify and sequence at each time point. Results The total number of clones from 3 patients with poor response to initial combined treatment of Lamivudine and Adefovir dipivoxil for chronic hepatitis B at each time point was 398. About patient S1 at baseline, genotype C accounting for 8.3% , genotype B, for 91.7% , so genotype B was in dominant （22/24）. But genotype C has gradually developed to 100% after treatment for 60 weeks. About patient S2 and S3 ,genotype B was the only type at baseline. However type B has gradually ＂drift＂ to type C during treatment. When treatment for 60 weeks, type C has taken the absolute advantage 75% for S2, and 100% for S3. Conclusions The cloning and sequencing can represent the overall genotype level better. HBV genotype has.performed the evolution trend that genotype has drifted from B to C during long - term drug pressure, which is the main reason for poor response to initial combined treatment of Lamivudine and Adefovir dipivoxil for chronic hepatitis B.