Drug-Resistance Associated Mutations in Polymerase (P) Gene of Hepatitis B Virus Isolated From Malaysian HBV Carriers

BACKGROUND Mutations in the polymerase (P) gene of hepatitis B virus are often associated with drug resistance. The pattern of mutations varies geographically, thus giving rise to genotypes diversity. OBJECTIVES This study was carried out to detect mutations in P gene of hepatitis B virus isolated from Malaysian HBV carriers. MATERIALS AND METHODS A total of 58 sera samples were analyzed by PCR and sequencing, of which the P gene of isolated HBV was successfully amplified and sequenced from 40 samples. RESULTS Genotyping of these samples revealed that the predominant genotype was genotype C (22/40, 55.0%), followed by genotype B (17/40, 42.5%), and only 1 sample showed genotype D (2.5%). A number of significant drug resistant mutations were found in five patients including S202I, N236T, M250L, L180M/V, M204I, A181T, T184G, M250V, and V173L. Of these, L180M/V and M204I were most frequently detected (80%) and associated with lamivudine in combination with emtricitabine and telbivudine drug resistance. Association with age, sex, and clinical symptoms revealed that these patients were all male, mid to elderly age and almost all hadcirrhotic liver disease. CONCLUSIONS Detection and surveillance of the significant sites of mutations in HBV is crucial for clinicians to decide on the choice of antiviral treatment and further management of hepatitis B carriers.