Analysis of the polymerase gene of HBV virus

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The mutational pattern of the polymerase gene in HBV carriers under lamivudine (LAM) treatment was examined. Mutation in the rt204 of the polymerase gene (so called YMDD motif) was detected in 28% of patients with persistently negative for HBVDNA. These latent mutations without clinically obvious breakthrough, progressed to overt viral breakthrough in 80% of patients within 2 years of LAM treatment, 33% of patients with 3 to 5 years of LAM treatment and 0% of patients with 5 or more years of LAM treatment In addition some patients had mutation in the rt180, which was positively correlated with subsequent development of viral breakthrough. Mutations in rt80 was also frequently observed but was not related to clinical outcomes.In the analysis of patients with long term entecavir therapy for LAM resistant virus, those without clearance of HBV at week 24 had higher risk of developing resistant virus. The rt204V mutation may be related to higher risk of resistance, which need further investigations.