INTRODUCTION: Mutations of hepatitis B virus (HBV) polymerase, especially occurring at the highly conserved YMDD region, are related to resistance to lamivudine. Although these mutations are frequently secondary to lamivudine use, they can also occur naturally. The aim of the present study was to determine the prevalence of YMDD variants that exist naturally in patients who are inactive HBV carriers. METHODS: Seventy-one adult inactive HBV carriers were studied. All of the patients were confirmed to have maintained normal alanine aminotransferase (ALT) values for one or more years by monitoring serum ALT levels at 3-monthly intervals. None of the patients received interferon or antiviral agents. YMDD variants were analyzed by the HBV Drug Resistance Line Probe assay (Inno-Lipa HBV-DR). RESULTS: YMDD variants were detected in 13 (18.3%) of the 71 anti-HBe positive inactive HBV carriers. Of the 13 patients, 10 (76.9%) also had accompanying L180M mutation. The combination of wild type and YMDD variant HBV was present in 11 of 13 patients. In two patients, only YIDD and/or YVDD variants plus L180M were detected without the presence of wild YMDD motif. CONCLUSION: Naturally occurring YMDD motif variants were detected at a high rate in a group of lamivudine-untreated inactive HBV carriers.
INTRODUCTION: Mutations of hepatitis B virus (HBV) polymerase, especially occurring at the highly conserved YMDD region, are related to resistance to lamivudine. Although these mutations are frequently secondary to lamivudine use, they can also occur naturally. The aim of the present study was to determine the prevalence of YMDD variants that exist naturally in patients who are inactive HBV carriers. METHODS: Seventy-one adult inactive HBV carriers were studied. All of the patients were confirmed to have maintained normal alanine aminotransferase (ALT) values for one or more years by monitoring serum ALT levels at 3-monthly intervals. None of the patients received interferon or antiviral agents. YMDD variants were analyzed by the HBV Drug Resistance Line Probe assay (Inno-Lipa HBV-DR). RESULTS: YMDD variants were detected in 13 (18.3%) of the 71 anti-HBe positive inactive HBV carriers. Of the 13 patients, 10 (76.9%) also had accompanying L180M mutation. The combination of wild type and YMDD variant HBV was present in 11 of 13 patients. In two patients, only YIDD and/or YVDD variants plus L180M were detected without the presence of wild YMDD motif. CONCLUSION: Naturally occurring YMDD motif variants were detected at a high rate in a group of lamivudine-untreated inactive HBV carriers.
Authors: Jie Fang; Michael J Wichroski; Steven M Levine; Carl J Baldick; Charles E Mazzucco; Ann W Walsh; Bernadette K Kienzle; Ronald E Rose; Kevin A Pokornowski; Richard J Colonno; Daniel J Tenney Journal: Antimicrob Agents Chemother Date: 2009-05-11 Impact factor: 5.191