Prevention and treatment of liver fibrosis based on pathogenesis.
Multiple agents have been proposed for the prevention and treatment of fibrosis. S-adenosylmethionine was reported to oppose CCl4-induced fibrosis in the rat, to attenuate the consequences of the ethanol-induced oxidative stress, and to decrease mortality in cirrhotics. Anti-inflammatory medications and agents that interfere with collagen synthesis, such as inhibitors of prolyl-4-hydroxylase and antioxidants, are also being tested. In nonhuman primates, polyenylphosphatidylcholine (PPC), extracted from soybeans, protected against alcohol-induced fibrosis and cirrhosis and prevented the associated hepatic phosphatidylcholine (PC) depletion by increasing 18:2 containing PC species; it also attenuated the transformation of stellate cells into collagen-producing transitional cells. Furthermore, it increased collagen breakdown, as shown in cultured stellate cells enriched with PPC or pure dilinoleoyl PC, the main PC species present in the extract. Because PPC and dilinoleoyl PC promote the breakdown of collagen, there is reasonable hope that 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 progression of the disease, but may also reverse pre-existing fibrosis, as demonstrated for CCl4-induced cirrhosis in the rat and as presently tested in an ongoing clinical trial.
Lieber
C S
CS
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center and Mount Sinai School of Medicine, New York 10468, USA. liebercs@aol.com
D000818:Animals; D002251:Carbon Tetrachloride; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000502:physiology; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology; D008103:Liver Cirrhosis / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced; D010713:Phosphatidylcholines / Q000627:therapeutic use; D051381:Rats
D005217:Fat Emulsions, Intravenous; D010713:Phosphatidylcholines; C005152:lipostabil; D003094:Collagen; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1