Therapy for hepatic fibrosis.

Although there is no established therapy for the fibrogenesis of hepatic cirrhosis, many potential therapies are now emerging. The requirements for the "perfect therapy" for hepatic fibrosis can be listed: (1) the pharmacologic agent should be active only in the liver; (2) its effect should be specific for collagen (or another critical extracellular matrix component); and (3) it should not be toxic. To date no agents fulfill these criteria. Of the agents we reviewed, only colchicine appears sufficiently safe for use outside of controlled clinical trials for cirrhotic patients whose underlying disease is not otherwise treatable. However, confirmation of the efficacy of colchicine in additional well-controlled clinical trials is still required. Agents such as collagen propeptides require extensive in vitro development, while trials in animal models are required for prolyl 4-hydroxylase inhibitors, proline analogues, and prostaglandins. For more developed agents, such as malotilate and gamma-interferon, there is now a need for well-designed long-term clinical trials.