Prevention and treatment of liver fibrosis based on pathogenesis

Multiple agents have been proposed for the prevention and treatment of fibr osis. S-adenosylmethionine was reported to oppose CCl4-induced fibrosis in the rat, to attenuate the consequences of the ethanol-induced oxidative str ess, and to decrease mortality in cirrhotics. Anti-inflammatory medications and agents that interfere with collagen synthesis, such as inhibitors of p rolyl-4-hydroxylase and antioxidants, are also being tested. In nonhuman pr imates, polyenylphosphatidylcholine (PPC), extracted from soybeans, protect ed against alcohol-induced fibrosis and cirrhosis and prevented the associa ted hepatic phosphatidylcholine (PC) depletion by increasing 18:2 containin g PC species; it also attenuated the transformation of stellate cells into collagen-producing transitional cells. Furthermore, it increased collagen b reakdown, as shown in cultured stellate cells enriched with PPC or pure dil inoleoyl PC, the main PC species present in the extract. Because PPC and di linoleoyl PC promote the breakdown of collagen, there is reasonable hope th at this treatment may be useful for the management of fibrosis of alcoholic , as well as nonalcoholic, etiologies and that it may affect not only the p rogression of the disease, but may also reverse pre-existing fibrosis, as d emonstrated for CCl4-induced cirrhosis in the rat and as presently tested i n an ongoing clinical trial.