Methotrexate Hepatotoxicity and the Impact of Nonalcoholic Fatty Liver Disease

Am J Med Sci. 2017 Aug;354(2):172-181. doi: 10.1016/j.amjms.2017.03.014. Epub 2017 Mar 14.

Abstract

Methotrexate (MTX) is commonly used to treat individuals with rheumatological and dermatologic disorders. Current American College of Rheumatology (ACR) and American Association of Dermatology (AAD) guidelines identify diabetes and obesity as risk factors for MTX-induced liver injury. Both diabetes and obesity are components of the metabolic syndrome, and are also risk factors for nonalcoholic fatty liver disease (NAFLD). NAFLD affects approximately 40% of the U.S. population, and those with more advanced NAFLD (i.e., nonalcoholic steatohepatitis with or without fibrosis) are likely to develop progressive liver disease. As such, individuals who are treated with MTX may need to be screened for advanced NAFLD, as this may put them at an increased risk of MTX-induced liver injury. In this mini-review, we review the current ACR and AAD guidelines on MTX hepatotoxicity, discuss the evidence (or lack thereof) of the impact of metabolic risk factors on MTX-induced liver injury and highlight the areas that need further research.

Keywords: Chronic liver disease; Drug; Hepatotoxicity; Metabolic; Nonalcoholic steatohepatitis.

Publication types

  • Review

MeSH terms

  • Antirheumatic Agents / adverse effects*
  • Chemical and Drug Induced Liver Injury / etiology*
  • Dermatologic Agents / adverse effects*
  • Diabetes Mellitus / physiopathology
  • Humans
  • Metabolic Syndrome / physiopathology*
  • Methotrexate / adverse effects*
  • Non-alcoholic Fatty Liver Disease / chemically induced*
  • Obesity / complications
  • Risk Factors

Substances

  • Antirheumatic Agents
  • Dermatologic Agents
  • Methotrexate