Acetaminophen-Induced Liver Damage in Hepatic Steatosis

Clin Pharmacol Ther. 2020 May;107(5):1068-1081. doi: 10.1002/cpt.1701. Epub 2019 Dec 6.

Abstract

One of the most used painkillers is acetaminophen (APAP), which is safe at the right dose. However, several studies have described populations susceptible to APAP-induced liver damage, mainly in livers with steatosis. Thus, clinicians should consider the presence of obesity and other chronic liver diseases like nonalcoholic fatty liver disease (NAFLD) when indicating treatment with APAP. Liver damage from this drug is generated through its metabolite N-acetyl-p-benzoquinone imine, which is detoxified with glutathione (GSH). Prior depletion of GSH in steatotic hepatocytes plays a key role in APAP-induced hepatotoxicity in people with obesity and NAFLD. The knowledge about the damage to the liver or APAP in susceptible people like the obese and those with NAFLD is of great relevance for the sanitary sector because it would imply strategies of different therapeutic approach in such patients. This paper reviews the role of APAP in liver damage in the presence of obesity, NAFLD, and nonalcoholic steatohepatitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects*
  • Acetaminophen / pharmacokinetics
  • Animals
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Glutathione / metabolism
  • Hepatocytes / pathology
  • Humans
  • Non-alcoholic Fatty Liver Disease / complications*
  • Obesity / complications
  • Risk Factors

Substances

  • Acetaminophen
  • Glutathione