Oxidation phenotyping in alcoholics with liver disease of varying severity.
The propensity to develop alcoholic cirrhosis is probably, at least in part, genetically determined. A striking similarity exists histologically between perhexiline and alcohol-related hepatitis and both are potentially precirrhotic lesions. Liver damage due to perhexiline is associated with impaired drug oxidation capacity which is genetically determined and tested by use of debrisoquine. Oxidation phenotyping might be used to predict susceptibility to perhexiline liver damage; it might also predict the potential to develop alcoholic cirrhosis. Oxidation phenotyping was therefore undertaken, using debrisoquine in 100 alcoholic patients, 30 of whom had only fatty liver despite prolonged alcohol abuse, while the remaining 70 had alcoholic hepatitis and/or cirrhosis. One hundred patients with nonalcoholic chronic liver disease served as controls. The number of patients with severely impaired drug oxidation capacity (poor metabolizer phenotype) was similar in the alcoholic group (8%) and the nonalcoholic control group (7%). In particular, the incidence of the poor metabolizer phenotype was similar in alcoholics with severe liver disease (10%) and in those with only fatty change (3%). There appears to be no association between the susceptibility to develop alcoholic cirrhosis and drug oxidizing capacity.
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003647:Debrisoquin / Q000031:analogs & derivatives / Q000378:metabolism*; D004285:Dogs; D005235:Fatty Liver, Alcoholic / Q000235:genetics; D005260:Female; D006519:Hepatitis, Alcoholic / Q000235:genetics; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics* / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype
D007546:Isoquinolines; C012359:4-hydroxydebrisoquin; D003577:Cytochrome P-450 Enzyme System; D003647:Debrisoquin