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Hepatotoxicity of Methotrexate in Rheumatic Diseases

  • Adverse Drug Experience Review
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Summary

Methotrexate-induced hepatotoxicity is well recognised in the treatment of leukaemia, psoriasis and rheumatoid arthritis. The pathological lesions are non-specific, consisting of fatty change, nuclear pleomerphism, hepatocyte necrosis, portal chronic inflammatory infiltrate, fibrosis and cirrhosis. The mechanism of liver injury is poorly understood; intracellular accumulation of methotrexate polyglutamate and consequent folate deletion are suspected to play a role. Early studies in psoriasis clearly established a relationship of the hepatic injury with the frequency of methotrexate administration. With weekly low dose therapy, however, consensus is lacking regarding the incidence of hepatotoxicity because studies have had disparate control groups, used variable dosage regimens and often failed to document pre-existing liver disease or categorised patients at risk, i.e. elderly patients, alcoholics and obese diabetiecs. Moreover, current methods of assessing the degree of hepatic injury are subjective, relying on interpretation by an experienced histopathologist. Preliminary evidence suggests less frequent and less severe hepatotoxicity occurs in patients with rheumotoid arthritis, probably as a result of lower methotrexate doses and better patient selection. Nevertheless unit the risk of serious liver disease is better definded it is recommended that patients have a pretreatment liver biopsy, a follow-up biopsy afetr a cumulative dose of 1500mg, and then biopsies approximately every 2 years in the absence of other evidence of liver disease or risk factors.

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  1. Flinders Medical Centre, and Repatriation Genera Hospital, Adelaide and Flinders University of South Australia, Adelaide, Australia

    Sumant Kevat,  Michael Ahern (Senior Lecturer in Rheumatology) & Pauline Hall

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  1. Sumant Kevat
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Kevat, S., Ahern, M. & Hall, P. Hepatotoxicity of Methotrexate in Rheumatic Diseases. Medical Toxicology 3, 197–208 (1988). https://doi.org/10.1007/BF03259882

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