Abstract: Objective To explore the clinical characteristics between patients with M204 and with M204/A181T mutation in HBV reverse transcriptase（rt）region. Methods Eighty-seven patients with rtM204 site mutation and forty-one patients with rtM204/rtA181T mutation were selected. The levels of HBsAg，HBV DNA and ALT were analyzed with statistic method. All the treatment history with nucleos（t）ide analogues（NA）were reviewed retrospectively. Results Compared to rtM204 site mutation, rtM204+rtA181T mutation did not lead to the decline of HBsAg（P=0.3020）and HBV DNA（P=0.5917）and higher ALT level（P=0.8001）；Moreover，the mono-therapy of lamivudine was easy to induce rtM204 site mutation（41.38%），while lamivudine swicthing to adefovir was easy to induce the rtM204+rtA181T mutation（34.15%）. Conclusion The NAs for patients with rtM204 site mutation and for patients with rtM204+rtA181T mutation were not the same，but the virological characteristics between them were not significantly different.

Key words: Hepatitis B, Hepatitis B virus, P gene, Mutation