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

Abstract

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.