Lamivudine (LMV) is still the most commonly used nucleoside analogue in majority of the world. Its administration rapidly leads to resistance associated with mutations in HBV polymerase. THE AIM of the study was to assess the prevalence, nature and the time of LMV resistant variants appearence during a long term therapy.
Patients and methods: Study was carried out among 175 chronic hepatitis B patients treated with LMV. HBsAg, HBeAg as well as anti-HBe antibodies were detected by enzyme immunosorbent assay and HBV-DNA quantification was performed by RT-PCR. Mutations in HBV polymerase gen were detected by PCR using specific primers and direct sequencing. Liver biopsies were performed in 138 patients to evaluate grading and staging of chronic hepatitis by Scheuer's classification.
Results: Mean pre-treatment viral load was comparable among HBeAg-positive and negative patients (4.24 x 10(8) vs. 1.26 x 10(8) IU/ml). Mutations in HBV polymerase gen were detected in 96 patients. After 5 years of LMV therapy the prevalence of mutations was 51.9% in HBeAg-positive and 56.1% in HBeAg-negative. The most common mutations were observed at position 180, followed by 204, 202, and 169 of HBV polymerase gen. After average treatment period of 25 months in HBeAg-positive and 35 months in HBeAg-negative additional mutation 204 was observed in 81% and 77% respectively.
Conclusions: Large majority of patients develop point mutations at positions 180 and 204 of HBV polymerase gene after 2 years of treatment with LMV. These mutations limit the efficacy of LMV but also yield cross-resistance with entecavir.