TY - JOUR
T1 - Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol
T2 - Analysis of instances of therapeutic misadventure
AU - Zimmerman, Hyman J.
AU - Maddrey, Willis C.
N1 - Funding Information:
* The registry of acetaminophen hepatic injury in alcohol consumers has received support from Whitehall Laboratories. It is part of a registry with broader attention to drug-induced injury that has been maintained by one of the authors (H.J.Z.) and is supported by grants from the Food and Drug Administration (1979 to 1981), Veterans Administration funds (1981 to 1989), Ciby-Geigy Col~poration, Basel, Switzerland, and Sandoz Pharmaceuticals, E Hanover, NJ (1989 to present).
PY - 1995/9
Y1 - 1995/9
N2 - Hepatic injury in alcoholics due to intake of acetaminophen (APAP or acetylparaaminophenol) with therapeutic intent has been reported, but the extent of the phenomenon is not clear, pertinent details of the association remain insufficiently clarified, and the importance of the phenomenon is not widely appreciated. The present report describes 67 patients who developed hepatic injury after ingestion of APAP with therapeutic intent. All were regular users of alcohol. Sixty-four percent of the patients were considered to be "alcoholic" or reported intakes greater than 80 g/d, 35% took 60 g/d or less, and the remainder were vague in their reporting. Doses of APAP were in the "nontoxic" range (<6 g/d) in 60% of the group, within the recommended range (<4 g/ d) in 40%, and at 4.1 to 6 g/d in 20%. Characteristic feature was the towering level reached by aspartate transaminase (AST) with figures ranging from 3,000 to 48,000 IU in more than 90% of cases. Almost 20% of the patients died. The data on these patients were similar to 94 cases of injury from APAP taken with therapeutic intent reported in the literature. This study provides further evidence of hepatic injury in regular users of alcohol, especially chronic alcoholics, who take APAP with therapeutic intent. Susceptibility is presumably caused by induction of cytochrome P-4502EI by ethanol and by depletion of glutathione (GSH) because of the effects of alcohol, the malnutrition often associated with alcoholism, and the depletion associated with chronic use of APAP and impaired glucuronidation caused by fasting perhaps as well. The syndrome of liver injury is distinctive, marked by uniquely elevated levels of AST, and poses a significant threat. A greater awareness of the phenomenon by the medical and lay community is essential.
AB - Hepatic injury in alcoholics due to intake of acetaminophen (APAP or acetylparaaminophenol) with therapeutic intent has been reported, but the extent of the phenomenon is not clear, pertinent details of the association remain insufficiently clarified, and the importance of the phenomenon is not widely appreciated. The present report describes 67 patients who developed hepatic injury after ingestion of APAP with therapeutic intent. All were regular users of alcohol. Sixty-four percent of the patients were considered to be "alcoholic" or reported intakes greater than 80 g/d, 35% took 60 g/d or less, and the remainder were vague in their reporting. Doses of APAP were in the "nontoxic" range (<6 g/d) in 60% of the group, within the recommended range (<4 g/ d) in 40%, and at 4.1 to 6 g/d in 20%. Characteristic feature was the towering level reached by aspartate transaminase (AST) with figures ranging from 3,000 to 48,000 IU in more than 90% of cases. Almost 20% of the patients died. The data on these patients were similar to 94 cases of injury from APAP taken with therapeutic intent reported in the literature. This study provides further evidence of hepatic injury in regular users of alcohol, especially chronic alcoholics, who take APAP with therapeutic intent. Susceptibility is presumably caused by induction of cytochrome P-4502EI by ethanol and by depletion of glutathione (GSH) because of the effects of alcohol, the malnutrition often associated with alcoholism, and the depletion associated with chronic use of APAP and impaired glucuronidation caused by fasting perhaps as well. The syndrome of liver injury is distinctive, marked by uniquely elevated levels of AST, and poses a significant threat. A greater awareness of the phenomenon by the medical and lay community is essential.
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U2 - 10.1016/0270-9139(95)90295-3
DO - 10.1016/0270-9139(95)90295-3
M3 - Article
C2 - 7657281
AN - SCOPUS:0029083319
SN - 0270-9139
VL - 22
SP - 767
EP - 773
JO - Hepatology
JF - Hepatology
IS - 3
ER -