Mutation patterns in the RT region of hepatitis B virus P gene in patients treated with nucleoside/nucleotide analogs

Abstract

To analyze mutation patterns in the RT region of hepatitis B virus (HBV) P gene in patients treated with nucleoside or nucleotide analogs. Viral DNA was extracted from 227 serum samples of chronic hepatitis B patients from September, 2005 to March, 2007. The RT region of HBV P gene was PCR-amplified and sequenced. Known resistant mutations were found in 111 cases (48.9%) among 227 samples, 75 cases with clear therapy history. Novel mutations, including A222T, L229V and S256C, were also found. The incidence of multi-drug resistance in patients sequentially treated with lamivudine and adefovir was 25% (4/16), and none of the patients treated with lamivudine plus adefovir in combination shown multi-drug resistance. The patterns of mutation is complex in nucleotide analogue treated patients. Switching to adefovir in lamivudine resistant patients may lead to multi-drug resistance. Novel mutations identified in this study need further investigation.