Association of acetaminophen hepatotoxicity with fasting and ethanol use

JAMA. 1994 Dec 21;272(23):1845-50. doi: 10.1001/jama.1994.03520230055038.


Objectives: To evaluate the association of fasting and alcohol use with hepatotoxicity from acetaminophen ingested for therapeutic reasons.

Design: Retrospective case series.

Setting: Hospitals of the University of Pittsburgh (Pa) Medical Center.

Patients: A total of 126,779 discharge summaries from January 1987 to July 1993 were reviewed using a comprehensive, whole-text-indexed medical database to identify all patients with acetaminophen ingestion and hepatotoxicity. These patients were categorized according to the intended acetaminophen use and dose of acetaminophen ingested.

Main outcomes measured: The independent variables of chronic alcohol use, recent alcohol use, and recent fasting were determined for all patients.

Results: Forty-nine patients with acetaminophen hepatotoxicity (aspartate aminotransferase > 1000 U/L) were identified. Twenty-one patients (43%) ingested acetaminophen for therapeutic purposes. All patients with hepatotoxicity took more than the recommended limit of 4 g/d. Recent fasting was more common than recent alcohol use among those who suffered hepatotoxicity after a dose of 4 to 10 g of acetaminophen per day (P = .02). Recent alcohol use was more common in the group who took more than 10 g/d than in those who took 4 to 10 g/d (P = .004).

Conclusion: Acetaminophen hepatotoxicity after a dose of 4 to 10 g/d was associated with fasting and less commonly with alcohol use. Patients who developed hepatoxicity after taking acetaminophen doses of greater than 10 g/d for therapeutic purposes were alcohol users. Acetaminophen hepatotoxicity after an overdose appears to be enhanced by fasting in addition to alcohol ingestion.

MeSH terms

  • Acetaminophen / adverse effects*
  • Acetaminophen / metabolism
  • Acetaminophen / poisoning
  • Adolescent
  • Adult
  • Aged
  • Alcohol Drinking / adverse effects
  • Alcoholism / complications*
  • Chemical and Drug Induced Liver Injury*
  • Drug Overdose / complications
  • Drug Synergism
  • Ethanol / adverse effects*
  • Ethanol / metabolism
  • Fasting / adverse effects*
  • Fasting / metabolism
  • Female
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Middle Aged
  • Retrospective Studies


  • Acetaminophen
  • Ethanol