IL-10 Reduces Fibrosis

IL-10 Reduces Fibrosis in Patients With Interferon-Refractory Hepatitis C

WESTPORT, Apr 26 (Reuters Health) - Administration of interleukin 10 (IL-10) reduces hepatic inflammation and liver fibrosis in the majority of patients with chronic hepatitis C who fail to respond to standard interferon therapy, according to data published in the April issue of Gastroenterology.

"Our findings suggest that IL-10 has an important role in chronic inflammation and fibrogenesis in this disease," Dr. David R. Nelson, of the University of Florida in Gainesville, and a multicenter team say in the report.

Dr. Nelson and his team assigned 24 patients with chronic hepatitis C that was unresponsive to prior interferon therapy to receive recombinant IL-10 at doses of 4 or 8 mcg/kg per day s.c. for 90 days. At the end of treatment, 19 of the 22 patients who completed the study had normal serum alanine aminotransferase levels. Moreover, hepatic inflammation scores decreased in 19 patients, and the reduction was 2 points or more in 11 patients.

Treatment with IL-10 also had a "striking" effect on liver fibrosis, the investigators say. In particular, IL-10 administration caused "reductions in serum levels of collagen IV, collagen VI, and hyaluronic acid, which are important constituents of the extracellular matrix." And IL-10 therapy was safe and well tolerated.

The mechanisms underlying the benefits of IL-10 in patients with interferon-refractory chronic hepatitis C are "complex," Dr. Nelson and colleagues comment. They suspect that at least part of the benefit is mediated by the inhibitory effect of IL-10 on the tumor necrosis factor system.

The results from this pilot trial "suggest that rIL-10 may be useful in the treatment of chronic hepatitis C and other chronic liver diseases that may eventually cause fibrosis and cirrhosis," the authors conclude. They note that further studies are already under way to confirm the safety and efficacy of long-term IL-10 therapy in this population.

Gastroenterology 2000;118:655-660

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