Alcoholic liver injury: pathogenesis and therapy in 2001.
Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of prevention and promising prospects for even more effective treatments. It continues to be important to replenish nutritional deficiencies when present but it is crucial to recognize that, because of the alcohol-induced disease process, some of the nutritional requirements change. For instance, methionine, one of the essential amino acids for humans, must be activated to SAMe but, in severe liver disease, the activity of the corresponding enzyme is depressed. Therefore, the resulting deficiencies and associated pathology can be attenuated by the administration of SAMe, but not by methionine. Similarly, phosphatidylethanolamine methyltransferase (PEMT) activity, which is important for hepatic phosphatidylcholine (PC) synthesis, is also depressed in alcoholic liver disease, therefore calling for administration of the products of the reaction. It might also be beneficial to add other compounds to such therapeutic regiment. Since free radical generation by the ethanol-induced CYP2E1 plays a key role in the oxidative stress, inhibitors of this enzyme have great promise. Several have been investigated experimentally and PPC is particularly interesting because of its innocuity. In view of the striking negative interaction between alcoholic liver injury and hepatitis C, an antiviral agent is eagerly awaited that, unlike Interferon, is not contraindicated in the alcoholic. Anti-inflammatory agents are also required. In addition to down-regulators of cytokines and end toxic are being considered. Finally, since excess drinking is the crux of the issue, anticraving agents should be incorporated in any contemplated therapeutic cocktail, in view of the recent promising results obtained with some of these agents such as naltrexone and acamprosate.
Lieber
C S
CS
Mount Sinai School of Medicine, Alcohol Research and Treatment Center, Section of Liver Disease and Nutrition, Bronx Veterans Affairs Medical Center, Bronx, NY 10468, USA. liebercs@aol.com
D000431:Ethanol / Q000009:adverse effects; D005235:Fatty Liver, Alcoholic / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000517:prevention & control / Q000628:therapy; D008108:Liver Diseases, Alcoholic / Q000209:etiology* / Q000628:therapy*; D009747:Nutritional Physiological Phenomena; D009752:Nutritional Status; D018384:Oxidative Stress; D014815:Vitamins / Q000627:therapeutic use
D014815:Vitamins; D000431:Ethanol