12 months lamivudine (100mg od) therapy improves liver histology: results of a placebo controlled multicentre study in Asia

Abstract

Phase II studies using lamivudine (2",3-dideoxy,3"-thiacytidine) demonstrated an excellent efficacy and safety profile with no major toxicities. To study whether longer term treatment would lead to histologic improvement, we initiated a placebo controlled study in adults with compensated chronic hepatitis B (HBsAg and HBeAg positive for >6m). Patients were randomised (2:2:1) to lamivudine 25mg (LAM25), lamivudine 100mg (LAM100) or placebo (PLB) given orally once daily for 12m. Efficacy was assessed by >_.2 point reduction in necro-inflammatory Knodell score. The results provided in this abstract are preliminary. Results: 358 Asian patients were randomised to PLB (73), LAM25 (142) and LAM100 (143). The groups were well matched at baseline; 73% male, median age 32y, median Knodell HAl score 7 and 5% cirrhotics, >95% patients were positive for HBV DNA and HBeAg and 68% had an abnormal ALT. Patients in the LAM100 group demonstrated the greatest histological improvement (66%) compared to either LAM25 (58%, p=NS) or PLB (30%, p<0.05). The LAM100 group also had the highest number of patients with a negative HBV DNA during treatment (96%) and normal ALT at the end of treatment (83%) compared to PLB (26% and 49% respectively). Conclusions: Lamivudine 100rag once daily treatment for ly was the most effective dosing regimen which significantly reduced necro-inflammatory activity compared to PLB (p<0.05) and induced ALT normalisation and HBV DNA negativity.