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David C. Whitcomb, MD, PhD; Geoffrey D. Block, MD, MPH

JAMA. 1994;272(23):1845-1850.

Abstract
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 126779 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.

(JAMA. 1994;272:1845-1850)

Author Affiliations
From the Division of Gastroenterology and Hepatology, Department of Medicine (Drs Whitcomb and Block), Department of Pathology (Dr Block), and Department of Cell Biology and Physiology (Dr Whitcomb), University of Pittsburgh, and the Department of Veterans Affairs Medical Center (Dr Whitcomb), Pittsburgh, Pa.

Footnotes
Dr Whitcomb has received travel expenses and a $1000 honorarium from McNeil Pharmaceuticals. No extramural funding was provided for this study.

Reprint requests to the Division of Gastroenterology and Hepatology, Presbyterian University Hospital, M2, DeSoto at O'Hara St, Pittsburgh, PA 15213-2582 (Dr Whitcomb).

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