Molecular Analysis of Hepatitis B Virus Reverse Transcriptase Domain for Mutations Associated with Viral Resistance in Pakistani Patients

Abstract

Objectives: Current study was designed to screen out the resistant mutations in reverse transcriptase (RT) domain of hepatitis B virus (HBV) genome from non-responder Pakistani patients. Materials and Methods: A total of 22 patients, receiving different nucleot(s)ide analogues were included in the study. RT domain of the virus from samples of non-responder patients was amplified and sequenced. Sequences were aligned and analyzed for RT domain mutations. Results: After 18 months, 18 patients were responder and 4 were non-responder. Mean alanine aminotransferase (ALT) and viral load of responder patients decreased significantly as compared to those of non-responder patients. Two of the 4 samples from nonresponders were successfully sequenced. Mutations rtY135S, rtI169P, rtV173P, rtL180I, rtA181V, rtT184Y and rtM204V were identified from the sample of patient 1, while rtL80V/rtL80G and rtY135S were identified from the sample of patient 2. Conclusion: Mutations rtY135S, rtI169P, rtV173P, rtL180I, rtA181V, rtT184Y, rtM204V, rtL80V/rtL80G, and rtY135S are present in genome of HBV circulating in Pakistani patients. These mutations give resistance to virus against lamivudine, telbivudine, adefovir, and partially resistance against entecavir. However, no mutation was found to be associated with the viral resistance against tenofovir.