The mutation analysis of the reverse transcriptase domain and enticavir for treatment in lamivudine-resistant chronic hepatitis B patients

Objective: To explore the characteristics of mutaition in HBV polymerase(P) gene reverse transcriptase region(RT region) and characterize the therapeutic efficacy of entecavir in lamivudine-resistant chronic hepatitis B(CHB) patients.Methods: This study involved 45 CHB patients who had received lamivudine treatment and developed clinical resistance to lamivudine.Direct sequencing of HBV reverse transcriptase region which was amplified by PCR was used to detect lamivudine genotypic resistance.Patients of CHB who had received lamivudine treatment and developed lamivudine resistance before switched to entecavir(1.0mg/d,monotherapy 48 weeks).Virological and serologic response and laboratory data of liver function of each patient enrolled were monitored every 12 weeks.As the control,a total of 30 chronic HBV infected patients in our hospital were treated with entecavir 0.5mg per day.Results: The major and the combined mutations including YMDD and rtL180M+rtM204V were detected in 45 lamivudine resistant patients,accounting for 71% and 42% respectively.Of the 45 lamivudine refractory CHB patients,40 had normal ALT levels(40IU/L) and undetectability in HBV DNA level(103 copies/ml) after 48 weeks of entecavir therapy with a dose of 1.0mg/d.There was no statistical significance between lamivudine refractory CHB patients and the controls after the entecavir treatment.Three of thirty HBeAg positive patients(10%) achieved HBeAg serconversion in 48 weeks.The percentage of HBeAg serconversion was significantly lower than that of the controls(P0.05).HBV DNA was decreased significantly more slowly than that of the controls during the process of entecavir treatment(P0.01).Conclusion: The major mutation forms of lamivudine-resistant is rtM204V/I through the analysis of the multiple sites at HBV P gene RT region.Entecavir therapy with a dosage of 1.0mg/d is effective in treating lamivudine-resistant chronic hepatitis B(CHB) patients.