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Current Gastroenterology Reports

, Volume 1, Issue 1, pp 42–49 | Cite as

Acetaminophen hepatotoxicity: An update

  • Craig J. McClain
  • Seth Price
  • Shirish Barve
  • Radhika Devalarja
  • Steven Shedlofsky
Article

Abstract

Acetaminophen is a widely used nonprescription analgesic and antipyretic agent. It is also a dose-related hepatotoxin that can cause fulminant liver failure when taken in massive overdoses or, much less commonly, at therapeutic doses in susceptible individuals. Persons who regularly consume alcohol or persons who have been fasting may be more susceptible to this hepatotoxicity. This liver injury is due not to the drug itself but to the formation of the toxic metabolite N-acetyl-p-benzoquinine imine generated through the cytochrome P-450 drug-metabolizing system. Normally, hepatic stores of glutathione combine with the toxic metabolite and prevent liver cell injury. When glutathione stores are depleted by overproduction of this metabolite, however, the reactive metabolite binds to liver cell proteins and causes hepatic necrosis. P-450 2E1 is induced by alcohol consumption and possibly starvation, and glutathione depletion can occur due to the inadequate nutrition occurring in chronic alcohol use or in starvation. Recent studies have shown that activated Kupffer cells and their secreted toxic agents such as cytokines may also play a role in this liver injury. This liver injury is characterized by extremely high levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (> 1000), and bad prognostic signs include severe prolongation of the prothrombin time, renal dysfunction, and, most importantly, acidosis. Nacetylcysteine is a highly effective antidote when given early (within 15 hours) of overdose. Some patients may develop such fulminant liver injury that they require transplantation. Unfortunately, many such patients have a course so rapid that a donor liver may not become available in time. Thus, both the medical community and the general public require a heightened understanding of this clinical problem in order to initiate prevention measures and to implement early therapeutic measures if an overdose situation occurs.

Keywords

Liver Injury Acetaminophen Acetami Fulminant Liver Failure Acetaminophen Overdose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Current Science Inc 1999

Authors and Affiliations

  • Craig J. McClain
    • 1
  • Seth Price
    • 1
  • Shirish Barve
    • 1
  • Radhika Devalarja
    • 1
  • Steven Shedlofsky
    • 1
  1. 1.University of Kentucky Medical CenterLexingtonUK

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