Acetaminophen Usage Patterns and Concentrations of Glutathione and γ‐Glutamyl Transferase in Alcoholic Subjects

Abstract

To determine if subjects with chronic alcoholism are predisposed to acetaminophen-induced hepatotoxicity, and to determine the contributing factors. Prospective cohort study. Community-based crisis intervention center. One hundred eighty-eight subjects who answered "yes" to at least one of the four questions on the CAGE (Cut down-Annoyed-Guilty-Eye-opener) questionnaire for identifying alcoholism, and 10 healthy volunteers (controls). A history, physical examination, urine toxicologic analysis, ethanol and drug therapy history, and venous blood samples were collected on all subjects. Venous blood was analyzed for a liver profile, prothrombin time, and total and oxidized glutathione concentrations. A significantly higher proportion of daily drinkers were regular daily users (29.2% [45/154] vs 11.8% [4/34], p=0.0497) as well as abusers (35.7% [55/154] vs 14.7% [5/34], p=0.0237) of acetaminophen compared with non daily drinkers. Alcoholic subjects with elevated gamma-glutamyl transferase (GGT >or= 51 U/L) levels had significantly lower median plasma glutathione concentrations (2.33 micromol/L, 95% confidence interval [CI] 1.74-2.69 micromol/L) compared with those of alcoholic subjects with normal GGT concentrations (5.97 micromol/L, 95% CI 4.39-7.03 micromol/L, p<0.0001) and healthy volunteers (6.59 micromol/L, 95% CI 4.79-9.65 micromol/L, p=0.0002). A significant inverse correlation was also noted between the GGT concentration and the plasma total glutathione concentration (r = -0.62, p<0.0001). None of the 188 subjects met all preset criteria for hepatotoxicity. Daily drinkers were more than twice as likely as non daily drinkers to be regular daily acetaminophen users and abusers. Alcoholic subjects with elevated GGT concentrations had significantly lower plasma total glutathione concentrations, and plasma total glutathione concentrations inversely correlated with GGT concentrations. Elevated GGT concentrations may be a clinical marker of depleted glutathione in alcoholic subjects. Acetaminophen-induced hepatotoxicity appears to be uncommon in alcoholic subjects, despite the 31.9% (60/188 patients) who took doses that are potentially hepatotoxic.