泛昔洛韦和胸腺肽联合治疗过程中乙肝病毒聚合酶基因突变谱分析  

B domain mutations in the polymerase gene of hepatitis B virus during combination therapy with thymosin α1 and famciclovir in Chinese asymptomatic HBV carriers

作　　者：侯金林[1] 王战会[1] 孙剑[1] 冯筱榕[1] 骆抗先[1] 廖家杰[2] 

机构地区：[1]广州第一军医大学南方医院,510515 [2]香港大学玛丽医学院

出　　处：《中华医学杂志》2000年第8期574-576,共3页National Medical Journal of China

基　　金：国家自然科学基金!资助项目 (39670 0 39);国家"九七三"课题

摘　　要：目的　探讨泛昔洛韦治疗过程中乙型肝炎病毒 (HBV)耐药性的产生与多聚酶基因变异的可能关系。方法　慢性HBV无症状携带者 2 9例 ,接受泛昔洛韦和胸腺肽联合治疗 ,15例单用胸腺肽治疗。所有患者治疗时间为半年 ,随访半年 ,收集每位患者治疗前、治疗中和治疗后半年系列血清标本 ,进行血生化、HBVDNA定量和HBV标志物等常规检测 ,同时应用PCR的方法扩增HBV聚合酶基因B区和C区序列 ,PCR产物直接测序或克隆后测序。结果　联合治疗组 9例发生聚合酶基因B区和 /或C区氨基酸突变 ,其中 5例为B区联合突变 ,例如 :HBVG5 18E或 /和G5 2 0C。而单用胸腺肽治疗组无一例发生聚合酶基因B区和 /或C区突变。联合治疗组中出现聚合酶基因变异的 9例中 ,7例出现HBVDNA反跳 ;未出现变异的 2 0例病例中只有 2例出现HBVDNA反跳 ,变异与HBVDNA反跳呈明显相关。结论　泛昔洛韦联合胸腺肽治疗过程中聚合酶基因变异是多位点的 ,主要集中于聚合酶基因B区。这一部位可能是HBV核苷类似物敏感性决定区域之一。Objective To identify ‘B domain’ mutations of polymerase gene and its relationship with drug resistance during treatment with famciclovir in Chinese chronic asymptomatic HBV carriers. Methods Sequential sera from 29 Chinese chronic HBeAg positive HBV carriers treated with combination therapy with thymosin α1 (Tα1) plus famciclovir and also from 15 cases treated with Tα1 alone, were studied. Nucleotide sequences encoding ‘B’ and ‘C domain’ of the HBV polymerase gene were determined by direct or cloning sequencing methods. Results Nine Tα1 plus FCV treated and none of the Tα1 treated patients developed mutations in the ‘B domain’ of polymerase gene which could result in amino acid changes. The development of ‘B domain’ mutations, during treatment, was significantly associated with HBV DNA rebound in those who received Tα1 plus FCV. Conclusions Mutations in FCV treated patients resulting in amino acid changes mainly cluster in the ‘B domain’ of polymerase gene rather than in YMDD motif. The presence of mutations is significantly associated with HBV DNA rebound during treatment.

关 键 词：慢性乙型肝炎 药物疗法 泛昔洛韦 胸腺肽 

分 类 号：R512.62[医药卫生—内科学]