Affordable Access

Publisher Website

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

Authors
Publisher
Elsevier B.V.
Publication Date
Volume
43
Issue
1
Identifiers
DOI: 10.1016/j.jhep.2005.02.021
Keywords
  • Viral Hepatitis
Disciplines
  • Design
  • Medicine

Abstract

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 (CI), 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× 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.

There are no comments yet on this publication. Be the first to share your thoughts.