Genotypes and resistance loci in patients with chronic hepatitis B achieving virologic breakthrough in treatment with lamivudine combined with adefovir after developing drug resistance in treatment with lamivudine alone

Objective To investigate the genotypes and resistance loci in patients with chronic hepatitis B( CHB) achieving virologic breakthrough in the treatment with lamivudine( LAM) combined with adefovir( ADV) after developing drug resistance in the treatment with LAM alone. Methods A total of 89 CHB patients who were admitted to Henan Provincial People's Hospital and treated with LAM and ADV as the antiviral therapy after developing drug resistance in the treatment with LAM alone from June 2010 to June 2013 were enrolled,and their serum samples were collected. Quantitative real- time PCR was used for hepatitis B virus( HBV) detection,and sequencing was applied to determine the genotype and detect the resistance loci rt N236 T,rt A181 V,rt M204 V,and rt L180 M. The t- test was applied for comparison of continuous data between groups,and the chi- square test was applied for comparison of categorical data between groups. Results LAM rt M204 V mutation was detected in all the 89 patients after treatment with LAM alone. After the combination therapy with LAM and ADV,ADV rt N236 T mutation was detected in 9 patients,ADV rt A181 V mutation in 5 patients,and rt N236 T + rt A181 V mutation in 8 patients,with an overall ADV resistance rate of 24. 7%( 22 /89). As for HBV genotyping,82 patients had genotype C,and rt A181 V + rt N236 T mutation was detected in 8 patients; 7 patients had genotype B. Conclusion Compared with the patients with HBV genotype B,the patients with genotype C are more susceptible to rt A181 V + rt N236 T mutation during the combination therapy with LAM and ADV after developing drug resistance in the treatment with LAM alone.