Pattern of Mutations in Hepatitis B Virus Reverse Transcriptase Gene during Lamivudine Therapy in Patients with Chronic Hepatitis B Virus Infection

Background/Aims: Lamivudine resistant hepatitis B viruses (HBV) by mutations of YMDD motif in the HBV reverse transcirptase are very common in the patients with long-term lamivudine therapy. We investigated the pattern of mutations in and outside of YMDD motif of HBV reverse transcriptase gene during lamivudine therapy in patients with chronic hepatitis B infection. Methods: The study included 80 patients with chronic hepatitis B infection. To determine mutations in the HBV reverse transcriptase, the nucleotide 581-870 of the HBV reverse transcriptase was amplified and analyzed by direct sequencing method. Results: Amino acid changes were detected in 45 (56%) out of 80 patients. YMDD mutants were detected in 62% (28/45) and amino acid changes were detected outside of YMDD motif in 38% (17/45). M552I (82%, 23/28) was more common than M552V (18%, 5/28) in YMDD mutants. L528M was noted in 27% (12/45). F569Y (13%, 6/45), S571A (13%, 6/45), I572V (18%, 8/45) were common amino acid changes. Conclusions: Mutations were frequently detected outside of YMDD motif as well as YMDD motif of HBV reverse transcriptase gene in patients with lamivudine therapy. Most of the mutations in outside of YMDD motif were combined with YMDD mutants. No consistent mutation was found outside of YMDD motif in lamivudine resistant patients.