Title: Hepatitis B Virus (HBV) mutations during long-term therapy in chronic hepatitis B patients
Abstract: Background: Long-term lamivudine (LAM), adefovir (ADV) and entecavir (ETV) treatment has been found to induce the emergence of drug-resistant hepatitis B virus (HBV) in a significant number of patients with chronic hepatitis B infection. The aim of our study was to evaluate the LAM, ADV and ETV mutations detected in our patient group. Methods: Fifteen patients diagnosed with chronic hepatitis B were enrolled in this study. The patient group consisted of those who had received two years of treatment with nucleos(t)ide analogues. Patients were evaluated based on virologic and serologic response to therapy, and were classified as patients with a detectable level of HBV DNA and undetectable HBV DNA (<1.08 log copies/ml). The mutations associated with HBV drug resistance were investigated in patients with detectable HBV DNA. Due to resistance, in this group of patients treatment was change. Results: In our study group, four patients developed LAM-associated mutations (rtL180M+rtM204V, rtL180M+rtM204V/I, and 2 present rtM204I), three patients developed ADV-associated mutations (rtA181V+rtN236T; rtN236T and rtA181V), one patient developed ADV+LAM associated mutations (rtL180M+rtA181V+rtN236T) and other patient developed ETV-associated mutations (rtL180M+rtT184A+rtS202G+rtM204V). Beside the primary resistant mutations, various combinations of secondary and compensatory mutations conferring resistance to nucleos(t)ide analogues were detected in 5 (33%) patients. Conclusion: HBV treatment with nucleoside analogues results in the development of mutants strains, leading to drug resistance. These data suggest an early development of ETV resistance in patients with prior LAM and ADV resistance. Therefore genotypic resistance is important in monitoring HBV treatment. In conclusion, optimization of therapy combining LAM and ADV may be a good choice for patients with hepatitis B who have resistance mutations to ADV or LMV. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive