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

Abstract

Much progress has been made in the understanding of the pathogenesis of alcoholic 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 instance, methionine, one of the essential amino acids for humans, must be activated 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 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 the administration of the products of the reaction. Inasmuch as free radical generation by the ethanol-induced CYP2E1 plays a key role in the oxidative stress, inhibitors of this enzyme have great promise and PPC, which is presently being evaluated clinically, 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. Antiinflamatory agents may also be useful. In addition to steroids, down-regulators of cytokines and endotoxin are being considered. Finally, anticraving agents such as naltrexone or acamprosate should be incorporated into any contemplated therapeutic cocktail.

• Authors: C S Lieber
• Journal: Critical reviews in clinical laboratory sciences (Crit Rev Clin Lab Sci) Vol. 37 Issue 6 Pg. 551-84 (Dec 2000) ISSN: 1040-8363 [Print] England
• PMID: 11192332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S., Review)

Topics

• Alcoholism (complications)
• Humans
• Liver Diseases, Alcoholic (etiology, metabolism)
• Nutrition Disorders (etiology, metabolism)