Variability of reverse transcriptase gene in chronic hepatitis B patients treated with nucleos(t)ide analogue drugs

Objective The aim of this study was to analysis the variability of reverse transcriptase (RT) in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogue (NA) drugs. Methods Polymerase chain reaction (PCR) and direct-sequencing were performed to analysis the entire hepatitis B virus (HBV) RT gene of HBV isolates from 55 consecutive CHB patients treated with NA. Results Mutations were found at the 7 classical NA resistance (NAr) positions (rtL80, rtV173, rtL180, rtA181, rtM204, rtN236, rtM250), but not at other 4 classical NAr positions (rtI169, rtT184, rtA194, rtS202). Among the 55 HBV isolates, 31 (56.4%) harboured classical NAr mutations, the rtM204V/I was the major mutation type (27/31, 87.1%) in the patients treated with NA rtL80I was occurred in most of the patients with rtM204I (14/22, 63.6%). The rtL180 mol/L was often coexisted with the rtM204V (5/5, 100%). Non-classical mutations related to NAr were also found at other positions, including rtA222T, rtL229 F/S/W, rtS256C/G, rtQ267H.The rtA222T mutation had a highest percentage (40%, 22/55) in these non-classical mutation positions. Conclusions The patterns of mutation within RT gene are complex in CHB patients treated with NA drugs. In the RT gene of patients treated with NA drugs, there were also had other mutation positions, which might be associate with NA resistance. Monitoring HBV drug resistance mutation markers and patterns in patients treated with NA drugs is benefit to adjust the regimens timely in clinical therapy. Key words: Hepatitis B; Nucleotide; Drug resistance; Mutation