Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B


Dr S. Gaia, Molinette Hospital, C. Bramante 88, 10126 Turin, Italy.


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.