Author/Authors :
Poortahmasebi، Vahdat نويسنده Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Fakhari، Ehsan نويسنده Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Norouzi، Mehdi نويسنده Hepatitis B Molecular Laboratory, Department of Virology-School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Khamseh، Azam نويسنده Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Mahmoodi Karkhaneh، Masoud نويسنده Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Tavakoli، Ahmad نويسنده Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Jazayeri، Seyed Mohammad نويسنده Hepatitis B Molecular Laboratory-Department of Virology-School of Public Health-Tehran University of Medical Sciences, Tehran , , Malekzadeh، Reza نويسنده Digestive Disease Research Center, Shariati Hospital, Tehran, IR Iran , , Montazeri، Ghodratollah نويسنده Digestive Disease Research Centre, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran ,
Abstract :
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.
