A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987–1993)

doi:10.1016/0016-5085(95)90758-0

Gastroenterology

Volume 109, Issue 6, December 1995, Pages 1907-1916

https://doi.org/10.1016/0016-5085(95)90758-0 Get rights and content

Abstract

$Background & Aims:$ Five hundred sixty patients admitted between January 1, 1987, and December 31, 1993, with severe acetaminophen-induced hepatotoxicity were studied. The aim of this study was to identify why severe acetaminophen-induced hepatotoxicity still occurs and to determine how known risk factors and advances in management have affected the pattern of illness and outcome. $Methods:$ This was a retrospective study of the etiologic factors and the clinical course of all acetaminophen-related admissions. $Results:$ The number of admissions increased from 58 in 1987 to 123 in 1993. During the corresponding period, overall survival improved from just <50% to 78%. The percentage of admissions treated with N-acetylcysteine increased from 40% in 1987 to 83% in 1993. The frequency with which grade III or IV encephalopathy developed decreased from 62% in 1987 to 40% in 1993, and the percentage of these patients who developed cerebral edema decreased from 61% to 45% during the same period. There was an increase in both the number of patients transplanted and the survival of those managed medically. $Conclusions:$ Severe acetaminophen-induced hepatotoxicity remains a serious condition, but the increasing use of N-acetylcysteine, advances in medical management, and the increasing availability of transplantation have resulted in a significant improvement in survival rates.

References (37)

JG O'Grady et al.
Early indicators of prognosis in fulminant hepatic failure
Gastroenterology
(1989)
P Moldeus et al.
Effects of chronic ethanol administration on drug metabolism in isolated hepatocytes with emphasis on paracetamol activation
Biochem Pharmacol
(1980)
FJ Peterson et al.
Ethanol induction of acetaminophen toxicity and metabolism
Life Sci
(1980)
CR Scott et al.
Cysteamine treatment im paracetamol overdose
Lancet
(1975)
PM Harrison et al.
Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine
Lancet
(1990)
CO Record et al.
Disturbances in lactate metabolism in patients with liver damage due to paracetamol overdosage
Metabolism
(1981)
D Bihari et al.
Lactic acidosis in fulminant hepatic failure: some aspects of pathogenesis and prognosis
J Hepatol
(1985)
Office of Population Censuses and Surveys
Mortality statistics: accidents and violence
(1991)
JB Spooner et al.
Paracetamol overdose—facts not misconceptions
Pharm J
(1993)
LF Prescott
Effects of non-narcotic analgesics on the liver
Drugs
(1986)

TJ Meredith et al.

Why do patients still die from paracetamol poisoning?

BMJ

(1986)

R Goulding et al.

Poisoning with drugs and chemical substances

LF Prescott

Paracetamol overdosage

JM Tredger et al.

Metabolic basis for high paracetamol dosage without hepatic injury: a case study

Hum Exp Toxicol

(1995)

O Strubelt et al.

The influence of ethanol pretreatment on the effect of nine hepatotoxic agents

Acta Pharmacol Toxicol

(1978)

LB Seeff et al.

Acetaminophen hepatotoxicity in alcoholics; a therapeutic misadventure

Ann Intern Med

(1986)

S Sherlock

Nutrition and the alcoholic

Lancet

(1984)

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^☆

Dr. Makin is the recipient of a British Digestive Foundation Training Fellowship.

The authors thank Dr. John Spooner for his continuing input into this work and his helpful comments.

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A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987–1993)☆

Abstract

Gastroenterology

Biochem Pharmacol

Life Sci

Lancet

Lancet

Metabolism

J Hepatol

Mortality statistics: accidents and violence

Paracetamol overdose—facts not misconceptions

Pharm J

Effects of non-narcotic analgesics on the liver

Drugs

Why do patients still die from paracetamol poisoning?

BMJ

Poisoning with drugs and chemical substances

Paracetamol overdosage

Metabolic basis for high paracetamol dosage without hepatic injury: a case study

Hum Exp Toxicol

The influence of ethanol pretreatment on the effect of nine hepatotoxic agents

Acta Pharmacol Toxicol

Acetaminophen hepatotoxicity in alcoholics; a therapeutic misadventure

Ann Intern Med

Nutrition and the alcoholic

Lancet