Approaches to treatment of fibrogenesis in alcoholic liver disease.
Alcoholic hepatitis is associated with progressive hepatic fibrosis and the development of cirrhosis. The increased fibrosis is principally the result of increased collagen synthesis which exceeds lesser increases in collagen degradation. No proven therapy exists for progressive hepatic fibrosis in alcoholic liver disease. Sobriety increases long-term survival, but there is no evidence that it affects the process of fibrogenesis once initiated. Corticosteroids increase hospital survival in severe alcoholic hepatitis, while long-term propylthiouracil therapy increased survival in moderately severe alcoholic hepatitis. However, neither therapy was found to decrease hepatic fibrosis. By contrast, long-term therapy with colchicine improved survival and decreased hepatic fibrosis in a few patients with cirrhosis. Potential new therapies which have been shown to decrease fibrosis in animals or by cells in vitro include prostaglandin E2, gamma interferon, and inhibitors of proline hydroxylation.
Mezey
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Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D006519:Hepatitis, Alcoholic / Q000517:prevention & control; D006801:Humans; D006909:Hydroxyproline / Q000037:antagonists & inhibitors; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D008104:Liver Cirrhosis, Alcoholic / Q000473:pathology* / Q000517:prevention & control; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000473:pathology
D007371:Interferon-gamma; D003094:Collagen; D015232:Dinoprostone; D006909:Hydroxyproline