Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B
Article first published online: 15 JUL 2004
Alimentary Pharmacology & Therapeutics
Volume 20, Issue 3, pages 281–287, August 2004
How to Cite
Gaia, S., Marzano, A., Smedile, A., Barbon, V., Abate, M. L., Olivero, A., Lagget, M., Paganin, S., Fadda, M., Niro, G. and Rizzetto, M. (2004), Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B. Alimentary Pharmacology & Therapeutics, 20: 281–287. doi: 10.1111/j.1365-2036.2004.02073.x
- Issue published online: 15 JUL 2004
- Article first published online: 15 JUL 2004
- Accepted for publication 21 May 2004
Aim : To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B.
Methods : Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively.
Results : The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma.
Conclusion : Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.