Underlying mechanisms and treatment of acetaminophen‑induced liver injury (Review)

Mol Med Rep. 2025 Apr;31(4):106. doi: 10.3892/mmr.2025.13471. Epub 2025 Feb 28.

Abstract

Acetaminophen (APAP) is safe at therapeutic doses; however, when ingested in excess, it accumulates in the liver and leads to severe hepatotoxicity, which in turn may trigger acute liver failure (ALF). This is known as APAP poisoning and is a major type of drug‑related liver injury. In the United States, APAP poisoning accounts for ≥50% of the total number of ALF cases, making it one of the most common triggers of ALF. According to the American Association for the Study of Liver Diseases, the incidence of APAP‑associated hepatotoxicity has increased over the past few decades; however, the mechanism underlying liver injury due to APAP poisoning has remained inconclusive. The present study aims to comprehensively review and summarize the latest research progress on the mechanism of APAP‑induced liver injury, and to provide scientific and effective guidance for the clinical treatment of APAP poisoning through in‑depth analysis of the metabolic pathways, toxicity‑producing mechanisms and possible protective mechanisms of APAP in the liver.

Keywords: acetaminophen; drug‑induced liver injury; mechanism; treatment.

Publication types

  • Review

MeSH terms

  • Acetaminophen* / adverse effects
  • Analgesics, Non-Narcotic* / adverse effects
  • Animals
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Chemical and Drug Induced Liver Injury* / pathology
  • Chemical and Drug Induced Liver Injury* / therapy
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology

Substances

  • Acetaminophen
  • Analgesics, Non-Narcotic