Lamivudine resistance in patients with chronic hepatitis B: Role of clinical and virological factors
Article first published online: 16 AUG 2006
Journal of Gastroenterology and Hepatology
Volume 22, Issue 7, pages 1078–1085, July 2007
How to Cite
Thompson, A. J. V., Ayres, A., Yuen, L., Bartholomeusz, A., Bowden, D. S., Iser, D. M., Chen, R. Y. M., Demediuk, B., Shaw, G., Bell, S. J., Watson, K. J. R., Locarnini, S. A. and Desmond, P. V. (2007), Lamivudine resistance in patients with chronic hepatitis B: Role of clinical and virological factors. Journal of Gastroenterology and Hepatology, 22: 1078–1085. doi: 10.1111/j.1440-1746.2006.04630.x
- Issue published online: 16 AUG 2006
- Article first published online: 16 AUG 2006
- Accepted for publication 13 March 2006.
- chronic hepatitis B;
- HBe antigen;
- lamivudine-resistant mutation;
- viral load
Background: Lamivudine resistance is associated with long-term monotherapy for chronic hepatitis B and can lead to potentially serious clinical consequences. Scant information exists regarding the influence of hepatitis B virus variants in the development of resistance. The present study was designed to identify factors predictive of lamivudine resistance, with a particular focus on the role of precore and basal core promoter variants in the setting of hepatitis B e antigen-negative disease.
Methods: Eighty-five patients, representing four major genotypes, were followed prospectively on lamivudine therapy. Resistance was defined as an increase in viral load, with polymerase gene sequencing confirming a lamivudine resistance mutation. Median follow up was 19 months (6–54 months). The Cox proportional hazards model was used to determine variables independently predicting for the early onset of lamivudine resistance.
Results: The rate of lamivudine resistance was 6%, 31% and 51% at 12, 24 and 48 months, respectively. Multivariate analysis identified the precore variant, high baseline alanine aminotransferase (ALT), and persistent viremia (at 6 months) as independent predictors of the early development of lamivudine resistance, with rate ratios of 4.93 (95% confidence interval [CI]: 1.32–18.5), 1.22 (95%CI: 1.08–1.49), and 4.73 (95%CI: 1.49–15.0), respectively (P < 0.05). Female sex predicted early resistance (rate ratio 5.27 [95%CI: 1.23–22.5, P < 0.05]) although numbers were small (n = 12). Genotype did not influence treatment response nor time to onset of resistance.
Conclusion: Patients with precore variant hepatitis B virus are likely to develop lamivudine resistance early and should be considered for alternate first-line monotherapy. In the future, combination antiviral therapy may limit the development of resistance.