Hepatic, metabolic, and nutritional disorders of alcoholism: From pathogenesis to therapy

Much progress has been made in the understanding of the pathogenesis of alc oholic liver disease, resulting in an improvement in treatment. Nutritional deficiencies should be corrected when present but, because of the alcohol- induced disease process, some of the nutritional requirements change. For i nstance, methionine, one of the essential amino acids for humans, must be a ctivated to S-adenosylmethionine (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 administrat ion of SAMe, but not by methionine. Similarly, phosphatidylethanolamine met hyltransferase (PEMT) activity, which is important for hepatic phosphatidyl choline (PC) synthesis, is also depressed in alcoholic liver disease, there fore calling for the administration of the products of the reaction. Inasmu ch as free radical generation by the ethanol-induced CYP2E1 plays a key rol e in the oxidative stress, inhibitors of this enzyme have great promise and PPC, which is presently being evaluated clinically, is particularly intere sting because of its innocuity. In view of the striking negative interactio n between alcoholic Liver injury and hepatitis C, an antiviral agent is eag erly awaited that, unlike Interferon, is not contraindicated in the alcohol ic. Antiinflamatory agents may also be useful. In addition to steroids, dow n-regulators of cytokines and endotoxin are being considered. Finally, anti craving agents such as naltrexone or acamprosate should be incorporated int o any contemplated therapeutic cocktail.