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Korean J Hepatol > Volume 8(4); 2002 > Article
The Korean Journal of Hepatology 2002;8(4): 405-417.
Clinical and Virologic Characteristics of Lamivudine Resistance in HBV-associated Chronic Liver Disease
Sun Suk Kim, M.D., Moon Gi Chung, M.D., Ki Tak Ju, M.D., Dong Kyun Park, M.D. Oh Sang Kwon, M.D.,Yang Suh Koo, M.D., Yu Kyung Kim, M.D., Duck Ju Choi, M.D. Yu Jin Hwang, Ph.D.* and Ju Hyun Kim, M.D.
Department of Internal Medicine, Laboratory of Molecular Biology*, Gachon Medical School, Gil Medical Center, Inchon, Korea
Abstract

Background/Aims:
Lamivudine therapy in chronic hepatitis B has been shown to be effective in inhibiting HBV replication. However, lamivudine resistance has been developed with prolonged use. We studied to etermine the prevalence, predictive factors, and clinical outcomes of lamivudine resistance. Mutations in YMDD motif of HBV polymerase, which have been associated with lamivudine resistance, were also assessed.
Methods:
170 patients with HBV-associated chronic liver disease who have received lamivudine for at least one year, were studied. The clinical, biochemical, and virologic characteristics were analyzed and compared according to presence (resistance group) or absence (non-resistance group) of DNA breakthrough. Their clinical outcomes were regularly followed. Stored sera before treatment and after DNA breakthrough were examined for detection of HBV polymerase mutation by direct sequencing and/or RFLP.
Results:
Cumulative rates of lamivudine resistance after one and two years of treatment were 11% and 34%, respectively. In the resistance group, as compared to the non-resistance group, age, the presence of HBeAg before treatment, and disappearance of HBeAg during treatment, were significantly different. The predictive factors associated with lamivudine resistance were not found. ALT and HBV-DNA level after lamivudine resistance was variable, but jaundice or hepatic failure was absent. Mutation in YMDD motif was detected in 73% and other variable mutations were detected before treatment and after DNA breakthrough.
Conclusions:
Lamivudine resistance increases the longer the duration of treatment and clinical outcomes are variable. The mutation in YMDD motif was found in about 2/3 of cases. Other causes for lamivudine resistance may be considered. (Korean J Hepatol 2002;8:405-417)
KeyWords: Hepatitis/Viral/Chronic Hepatitis B, Lamivudine resistance, YMDD mutant, Breakthrough, HBV polymerase mutation
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