Clinical

Lamivudine slows progression of chronic hepatitis B with advanced fibrosis

Last Updated: 2004-10-06 17:00:24 -0400 (Reuters Health)

NEW YORK (Reuters Health) - By reducing the occurrence of hepatic decompensation and the risk of liver cancer, lamivudine therapy delays the progression of chronic hepatitis B with advanced fibrosis or cirrhosis, new research indicates.

The findings, which appear in The New England Journal of Medicine for October 7, are based on a study of 651 patients who were randomized to receive lamivudine or placebo for up to 5 years. The study was terminated after a median period of 32.4 months after a clear difference in treatment efficacy was observed.

The main endpoint was the time to disease progression, which was defined as hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or liver disease-related death.

Treatment with lamivudine helped prevent hepatic decompensation and hepatocellular carcinoma, lead author Dr. Yun-Fan Liaw, from Chang Gung Memorial Hospital and University in Taipei and colleagues note.

Worsening of the Child-Pugh score was noted in 8.8% of control patients compared with just 3.4% of lamivudine-treated patients, the authors state (p = 0.02). Hepatocellular carcinoma occurred in 7.4% and 3.9% of patients in the control and lamivudine groups, respectively (p = 0.047).

Nearly half of the patients treated with lamivudine developed genotypic resistance YMDD mutations, the researchers note. The presence of such mutations was associated with a worsening of the Child-Pugh score.

The incidence and type of adverse events in each group were similar. Serious adverse events occurred in 12% of the treatment group and 18% of the placebo group.

The results suggest that lamivudine is effective in reducing liver complications in patients with chronic hepatitis B and advanced fibrosis or cirrhosis. "The magnitude of protection conferred by lamivudine is substantial, with a reduction of approximately 50% in disease progression during a median period of 32 months of treatment."

In a related editorial, Dr. Jack R. Wands, from Brown Medical School in Providence, Rhode Island, comments that "the use of potent antiviral agents such as lamivudine represents a major advance in the treatment of chronic HBV infection and slow the progression of severe liver disease to cirrhosis and hepatocellular carcinoma."

N Engl J Med 2004;1521-1531,1567-1570.