Lamivudine Resistance and Precore Variants in Iranian Patients With Chronic Hepatitis B: Correlation With Virological and Clinical Features

BACKGROUND Long-term lamivudine therapy, despite its initial effectiveness against hepatitis B virus (HBV), is associated with the emergence of drug resistance mutations in polymerase protein. OBJECTIVES The aim of the present study was to determine the prevalence of precore and lamivudine drug resistance mutations in lamivudine treated patients with chronic B hepatitis. PATIENTS AND METHODS Sequential sera were obtained from 88 chronic HBV carriers who received lamivudine for more than 24 months. Polymerase and precore regions were directly sequenced for these groups: I (before treatment), II, and III (12 and 24 months after treatment, respectively). RESULTS All patients (100%) were contained genotype D, subtype ayw2. One (1.1%), 12 (13.6%), and 22 (25%) members of groups I, II, and III had the replacement of either isoleucine or valine instead of methionine in tyrosine-methionine-aspartate-aspartate (YMDD) motif, respectively. The frequency of mutations from 0 time point to 12 and 24 months showed that there was an increasing trend between sequential samples (P < 0.001). In group I, 31 (35.2%); II, 36 (41.0%) and III, 41 (46.6%) members had the precore stop codon mutations. The frequency of mutations from 0 time point to 12 and 24 months showed that there was an ascending trend between sequential samples. Indeed, frequency of precore stop codon was significantly increased with the passage of time (P < 0.001). CONCLUSIONS Presence of drug resistance mutations among the patients was significant. Precore mutations were common amongst Iranian HBV chronic carriers under lamivudine therapy and these mutations were accompanied by clinical relapse.