Abstract :
Lamivudine for patients with chronic hepatitis B and advanced liver disease. Liaw YF, Sung JJY, Chow WC, Farrell G, Lee C-Z, Yuen H, et al.
Background
The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown.
Methods
Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to receive lamivudine (100 mg per day) or placebo for a maximum of five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive placebo. The primary end point was time to disease progression, defined by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or death related to liver disease. An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data.
Results
We randomly assigned 651 patients (98% Asian and 85% male) to receive lamivudine or placebo. The study was terminated after a median duration of treatment of 32.4 months (range, 0–42) owing to a significant difference between treatment groups in the number of end points reached. End points were reached by 7.8% of the patients receiving lamivudine and 17.7% of those receiving placebo (hazard ratio for disease progression, 0.45, P=0.0001). The Child–Pugh score increased in 3.4% of the patients receiving lamivudine and 8.8% of those receiving placebo (hazard ratio, 0.45, P=0.02), whereas hepatocellular carcinoma occurred in 3.9% of those in the lamivudine group and 7.4% of those in the placebo group (hazard ratio, 0.49; P=0.047). Genotypic resistance YMDD mutations developed in 49% of the patients treated with lamivudine, and the Child–Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine (7 vs 1%). Overall, 12% of the patients in the lamivudine group and 18% of the patients in the placebo group reported serious adverse events.
Conclusions
Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.
[Abstract reproduced by permission of New Engl J Med 2004; 351:1521–31].
