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 …

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２９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、ＨＢＶ ＤＮＡ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

B domain mutations in the polymerase gene of hepatitis B virus during combination therapy with thymosin alpha1 and famciclovir in Chinese asymptomatic HBV carriers]

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 alpha1 (Talpha1) plus famciclovir and also from 15 cases treated with Talpha1 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 Talpha1 plus FCV-treated and none of the Talpha1 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 Talpha1 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.