Liver diseases by alcohol and hepatitis C: early detection and new insights in pathogenesis lead to improved treatment.
Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of treatment. Therapy must include correction of nutritional deficiencies, while taking into account changes of nutritional requirements. Methionine is normally activated to S-adenosylmethionine (SAMe). However, in liver disease, the corresponding enzyme is depressed. The resulting deficiencies can be attenuated by the administration of SAMe but not by methionine. Similarly, phosphatidylethanolamine methyltransferase activity is depressed, but the lacking phosphatidylcholine (PC) can be administrated as polyenylphosphatidylcholine (PPC). Chronic ethanol consumption increases CYP2E1, resulting in increased generation of toxic acetaldehyde and free radicals, tolerance to ethanol and other drugs, and multiple ethanol-drug interactions. Experimentally, PPC opposes CYP2E1 induction and fibrosis. Alcoholism and hepatitis C infection commonly co-exist, with acceleration of fibrosis, cirrhosis, and hepatocellular carcinoma. PPC is being tested clinically as a corresponding antifibrotic agent. Available antiviral agents are contraindicated in the alcoholic. Anti-inflammatory agents, such as steroids, may be selectively useful. Finally, anticraving agents, such as naltrexone or acamprosate, should be part of therapy.
Lieber
C S
CS
Section of Liver Disease and Nutrition, Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, 130 West Kingsbridge Rd., Bronx, NY 10468, USA. liebercs@aol.com
D000431:Ethanol / Q000009:adverse effects; D005234:Fatty Liver / Q000139:chemically induced / Q000150:complications; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology; D009243:NAD / Q000096:biosynthesis; D009752:Nutritional Status; D018384:Oxidative Stress; D010713:Phosphatidylcholines / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000172:deficiency; D014801:Vitamin A / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism
D010713:Phosphatidylcholines; D019207:beta Carotene; D009243:NAD; D014801:Vitamin A; D000431:Ethanol; D012436:S-Adenosylmethionine