Efficacy of entecavir treatment for lamivudine-resistant hepatitis B over 3 years: Histological improvement or entecavir resistance?
Article first published online: 15 FEB 2009
© 2009 The Authors. Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 24, Issue 3, pages 429–435, March 2009
How to Cite
Suzuki, Y., Suzuki, F., Kawamura, Y., Yatsuji, H., Sezaki, H., Hosaka, T., Akuta, N., Kobayashi, M., Saitoh, S., Arase, Y., Ikeda, K., Kobayashi, M., Miyakawa, Y. and Kumada, H. (2009), Efficacy of entecavir treatment for lamivudine-resistant hepatitis B over 3 years: Histological improvement or entecavir resistance?. Journal of Gastroenterology and Hepatology, 24: 429–435. doi: 10.1111/j.1440-1746.2008.05760.x
- Issue published online: 23 MAR 2009
- Article first published online: 15 FEB 2009
- Accepted for publication 21 November 2008.
- chronic hepatitis;
- hepatitis B virus;
- YMDD mutants
Background and Aims: Long-term lamivudine therapy is required for patients with chronic hepatitis B, because hepatitis reappears frequently after it has withdrawn. However, hepatitis B virus (HBV) mutants resistant to lamivudine emerge frequently accompanied by breakthrough hepatitis.
Methods: Effects of entecavir were evaluated in 19 patients who had developed breakthrough hepatitis during lamivudine therapy for longer than 5 years. This study is a subgroup analysis of a previously reported study. Entecavir, in either 0.5 or 1.0 mg/day doses, was given to 10 and nine patients for 52 weeks, respectively, and then all received 1.0 mg/day entecavir for an additional 68–92 weeks.
Results: There were no differences in biochemical and virological responses in the two groups of patients with respect to the two different initial doses of entecavir. Serum levels of alanine aminotransferase were normalized in 17 (90%) patients, and hepatitis B e antigen (HBeAg) disappeared from the serum in two (14%) of the 14 patients who were HBeAg-positive before. Furthermore, a decrease in histological activity index score greater than 2 points was achieved in nine of the 11 (82%) patients in whom annual liver biopsies were performed during 3 years while they received entecavir. HBV mutants resistant to entecavir emerged in five of the 19 (26%) patients, and hepatitis flare occurred in two of them (40%).
Conclusion: Entecavir in the long term would be useful for histological improvement of breakthrough hepatitis induced by lamivudine-resistant HBV mutants in patients with chronic hepatitis B. However, the relatively high rate of entecavir resistance is a concern, and other strategies need to be considered when available.