Virus and transaminase levels determine the emergence of drug resistance during long-term lamivudine therapy in chronic hepatitis B

Background/Aims: The results of earlier studies on determinants for the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants (rtM204 I/V) were controversial. The aim was to evaluate the impact of viral factors, host factors, host-viral interaction and drug factor on the emergence of rtM204 I/V. Methods: 56 non-cirrhotic and 58 cirrhotic patients received lamivudine therapy for a median of 34 (12-60) months. Results: rtM204 I/V emerged in 37 noncirrhotic and 36 cirrhotic patients. Stepwise logistic regression analysis showed that baseline hepatitis B e antigen (HBeAg) status [odds ratio (OR), 7.728; 95 % confidental interval (0), 2.886-12.957; P=0.0026], HBV-DNA level (OR, 3.756; 95% CI, 1.058-5.089; P=0.0202), alanine transaminase (ALT) level (OR, 6.285; 95 % CI, 1.057-11.990; P = 0.00246) and treatment duration (OR, 19.88; 95 % CI, 8.652-31.762; P < 0.0004) were independent determinants for the emergence of rtM204 I/V. Further categorical analysis and correlation test disclosed that patients with HBeAg positivity, HBV-DNA > 500 pg/ml and ALT < 5 X upper limit of normal had significantly higher mutation rates. Conclusions: HBeAg status, HBV-DNA, ALT levels and treatment duration are the major determinants for the YMDD mutation during lamivudine therapy, and should be considered in designing the therapeutic strategy. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.