BACKGROUND: Despite significant progress in vaccine and therapeutic regimen, hepatitis B virus (HBV) infection remains one of the major diseases. Long-term use of lamivudine can induce the emergence of drug resistance. TRUGENE(TM) HBV Genotyping (Visible Genetics Inc., Ga, USA) is an assay that reports the viral genotype and mutations likely to confer resistance to antiviral therapy. In this study, we analyzed HBV genotype and mutations and correlated them with the histologic grade and stage of the liver disease to provide the useful information about the therapy of chronic liver disease. METHODS: HBV DNA was isolated from 86 patients with HBV-associated chronic liver diseases and analyzed by TRUGENE(TM) HBV Genotyping. Histologic grade and stage were correlated with RESULTS: HBV genotypes of 86 patients were all C (100%). Mutations associated with lamivudine resistance were detected in 10 patients (11.6%) and M204I (YIDD) mutant was the most common. Unknown mutation such as L180F was also detected. Statistical analysis showed that the number of coding changes at HBsAg region was significantly correlated with the lobular activity (P=0.01). CONCLUSIONS: All patients were genotype C and lamivudine resistant mutations were detected in 11.6%. L180F mutation, not known previously, was detected in one case. Number of coding changes at HBsAg region was significantly correlated with the lobular activity. It was considered that follow-up studies about the clinical significance of coding changes in HBsAg are needed, and that a further study such as in vitro transfection is necessary to confirm the possibility of a novel mutation of L180F.