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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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Busting the myth of methotrexate chronic hepatotoxicity

Vincent Di Martino1,2,3, Delphine Weil Verhoeven4,5,6, Frank Verhoeven7,8

  • 1Department of Hepatology, CHRU de Besançon, Besançon, France. vdimartino@chu-besancon.fr.

Nature Reviews. Rheumatology
|December 23, 2022
PubMed

Insights

Methotrexate, used for rheumatic diseases, carries liver risks, especially for those with non-alcoholic fatty liver disease (NAFLD). Careful monitoring and screening are crucial for safe, long-term methotrexate therapy.

Area of Science:

  • Rheumatology
  • Hepatology
  • Pharmacology

Background:

  • Methotrexate is a primary treatment for inflammatory rheumatic diseases, particularly rheumatoid arthritis.
  • Hepatotoxicity is a known concern with long-term methotrexate use.
  • Non-alcoholic fatty liver disease (NAFLD) prevalence and its interaction with methotrexate require careful consideration.

Purpose of the Study:

  • To evaluate methotrexate's liver toxicity in the context of current liver disease knowledge, especially NAFLD.
  • To understand the mechanisms of methotrexate-induced hepatotoxicity.
  • To provide practical guidance for screening and monitoring methotrexate therapy in patients with or at risk for chronic liver disease.

Main Methods:

  • Review of current understanding of liver disease pathogenesis and natural history, focusing on NAFLD.
  • Analysis of mechanisms underlying acute and chronic methotrexate hepatotoxicity.
  • Evaluation of available non-invasive liver fibrosis tests and liver biopsy for patient monitoring.

Main Results:

  • Patients with NAFLD face an elevated risk of methotrexate hepatotoxicity.
  • Methotrexate can exacerbate the progression of NAFLD.
  • Understanding hepatotoxicity mechanisms aids in interpreting liver enzyme elevations.

Conclusions:

  • Methotrexate hepatotoxicity must be assessed alongside NAFLD and other liver conditions.
  • Pretreatment screening and ongoing monitoring are essential for patients on long-term methotrexate, particularly those with liver disease risk factors.
  • Non-invasive tests and liver biopsy offer options for assessing liver health during methotrexate therapy.

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