A review of methotrexate-associated hepatotoxicity

J Dig Dis. 2014 Oct;15(10):517-24. doi: 10.1111/1751-2980.12184.


Methotrexate is effective not only in treating psoriasis and rheumatoid arthritis but also various other disorders. The use of methotrexate has been somewhat limited by concerns regarding its adverse effects, including its potential for hepatotoxicity. The purpose of this article is to provide an overview of methotrexate-associated hepatotoxicity, including risk factors, pathogenesis and recommendations for monitoring it by US, UK and European guidelines, as well as providing a brief overview of its mechanism of action and of high-dose methotrexate.

Keywords: hepatotoxicity; methotrexate; monitoring.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects*
  • Antirheumatic Agents / adverse effects*
  • Biomarkers / blood
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods
  • Folic Acid / therapeutic use
  • Humans
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Peptide Fragments / blood
  • Procollagen / blood
  • Risk Factors


  • Antimetabolites, Antineoplastic
  • Antirheumatic Agents
  • Biomarkers
  • Peptide Fragments
  • Procollagen
  • procollagen Type III-N-terminal peptide
  • Folic Acid
  • Methotrexate