Clinical

Etanercept fails to improve outcome of alcoholic hepatitis

Last Updated: 2008-12-31 12:02:28 -0400 (Reuters Health)

By Martha Kerr

NEW YORK (Reuters Health) - Although tumor necrosis factor (TNF)-alpha is a major player in the pathogenesis of alcoholic hepatitis, treatment with the TNF-alpha inhibitor etanercept does not improve outcome of the disease. In fact, it is associated with increased mortality, researchers report in the December issue of Gastroenterology.

A team led by Dr. Vijay H. Shah of the Mayo Clinic in Rochester, Minnesota, randomized 48 patients with moderate to severe alcoholic hepatitis, defined as a Model for End-stage Liver Disease (MELD) score of 15 or greater, to as many as six subcutaneous injections of either etanercept or placebo for 3 weeks. Primary endpoints were mortality at 1 and 6 months.

One-month mortality was 22.7% for placebo patients and 36.4% for the etanercept group, which was not a statistically significant difference. However, the 6-month mortality rate was significantly higher for patients on etanercept (57.7%) compared with patients on placebo (22.7%), for an adjusted odds ratio (OR) of 4.6.

Rates of infectious serious adverse events were significantly higher in the etanercept group (34.6%) compared with the placebo group (9.1%).

"Despite prior laboratory research studies that suggested that blocking the inflammatory molecule TNF would be beneficial in alcoholic liver disease, it was surprising that this treatment resulted in a higher mortality," Dr. Shah told Reuters Health.

"This may have been due to the treatment also blocking some of the potentially beneficial effects of tumor necrosis factor, such as liver regeneration and recovery, and supporting the ability of the body to fight off infections," the Mayo Clinic researcher said.

There remains no effective treatment for alcoholic hepatitis, a disease with a poor prognosis, Dr. Shah acknowledged.

"Some doctors do use corticosteroids or pentoxifylline for therapy, but these treatment approaches have not reached a broad consensus," he commented. "We provide conservative support therapy including optimizing nutrition, emphasizing abstinence from alcohol consumption, and treating infectious complications and complications of liver failure. Eventually, some of these patients may require liver transplantation if they can maintain abstinence and succeed in proper treatment of their alcoholism."

Dr. Shah added, "During the holiday times, with people drinking a lot, I think alcohol-related health issues should be of broad public interest."

Gastroenterology 2008;135:1953-1960.