CYP2E1 ACTIVITY IN PATIENTS WITH ALCOHOLIC LIVER-DISEASE

Background/Aims: In addition to the possible toxicological impact of c ytochrome P4502E1 (CYP2E1) in alcohol-induced liver damage, its activi ty can be regarded as a variable for drug action in patients with alco holic liver disease as CYP2E1. is involved in the metabolism of severa l drugs, for example, paracetamol and halogenated anesthetics, The pur pose of our study was to acquire detailed knowledge of CYP2E1 activity in patients with progressingly severe manifestations of alcoholic liv er disease. Methods: The concentration ratio of 6-hydroxy-chlorzoxazon e/chlorzoxazone in plasma 2 h after ingestion of 500 mg chlorzoxazone (so-called metabolic ratio) has been shown to reflect CYP2E1 activity in vivo, We examined CYP2E1 activity in 56 Caucasian inpatients with m inor (n=20), more pronounced (n=14) and severe alcoholic liver disease (n=22). Alcohol abusers were compared to healthy teetotallers (n=14). Results: Metabolic ratios were increased 3-fold in actively drinking (ethanol-induced) compared to abstaining (non-induced) patients with a lcoholic liver disease (1.19+/-0.84 vs. 0.44+/-0.45, mean+/-SD, (p<0.0 001), CYP2E1 activity was significantly lower in non-induced patients with severe alcoholic liver disease (0.19+/-0.10) than in healthy cont rols (0.50+/-0.28, p<0.01), abstaining alcohol abusers with minor (0.6 7+/-0.60, p<0.01) and more pronounced alcoholic liver disease (0.53+/- 0.31, p<0.01). When non-induced patients with alcoholic liver disease were arranged in progressing order of liver damage (minor, more pronou nced, severe alcoholic liver disease), there was a significant decline in CYP2E1 activity (p=0.0008). Conclusions: In non-induced patients, CYP2E1 activity decreases in line with severity of alcoholic liver dis ease, CYP2E1-mediated drug metabolism is significantly impaired in sev ere alcoholic liver disease.