Pathogenesis and treatment of liver fibrosis in alcoholics: 1996 update.
Fibrosis is a common end stage for most chronic liver diseases. It results from an imbalance between collagen production and degradation. One promising approach for prevention and treatment is the stimulation of collagenolytic processes. In nonhuman primates it was found that polyenylphosphatidylcholine (PPC), extracted from soybeans, protects against alcohol-induced fibrosis and cirrhosis and prevents the associated hepatic phosphatidylcholine (PC) depletion by increasing 18:2-containing PC species; it also attenuates the transformation of lipocytes into collagen-producing transitional cells. Furthermore, it increases collagen breakdown, as shown in cultured lipocytes enriched with pure dilinoleoyl PC (18:2-18:2 PC), the main PC species present in the extract, which may be the active ingredient. Since PC appears to promote the breakdown of collagen, there is reasonable hope that this treatment may affect not only the progression of the disease, but may also reverse preexisting fibrosis, as demonstrated for CCl4-induced cirrhosis in the rat. Therefore, PPC may be useful for the management of fibrosis of alcoholic and nonalcoholic etiologies as well. S-Adenosylmethionine opposes CCl4-induced fibrosis and can affect some of the consequences of the ethanol-induced oxidative stress in experimental animals and in man. Anti-inflammatory medications (corticosteroids, colchicine) are also being used and agents that interfere with collagen synthesis, such as inhibitors of prolyl-4-hydroxylase and antioxidants, are being tested.
Lieber
C S
CS
Section of Liver Disease, Bronx VA Medical Center, Mount Sinai School of Medicine, New York, N.Y., USA.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002251:Carbon Tetrachloride / Q000009:adverse effects; D003078:Colchicine / Q000627:therapeutic use; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy; D018384:Oxidative Stress / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism / Q000627:therapeutic use; D011323:Primates; D011393:Procollagen-Proline Dioxygenase / Q000627:therapeutic use; D051381:Rats; D012436:S-Adenosylmethionine / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D010713:Phosphatidylcholines; C005152:lipostabil; C002448:1,2-linoleoylphosphatidylcholine; D012436:S-Adenosylmethionine; D003094:Collagen; D002251:Carbon Tetrachloride; D011393:Procollagen-Proline Dioxygenase; D003078:Colchicine