Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis

Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis

It has long been believed that methotrexate in therapeutic doses causes progressive liver injury resulting in advanced fibrosis and cirrhosis. Historically, this was a common indication for serial liver biopsy. However, new evidence suggests that methotrexate may not be a direct cause of liver injur...

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Bibliographic Details
Published in:Journal of Investigative Medicine Vol. 70; no. 7; pp. 1452 - 1460
Main Authors: Cheema, Hira Imad, Haselow, Dirk, Dranoff, Jonathan Ankin
Format: Journal Article Book Review
Language:English
Published: Los Angeles, CA BMJ Publishing Group Ltd 01-10-2022
SAGE Publications
Sage Publications Ltd
Subjects:
Adenosine
Biopsy
Blood & organ donations
Body mass index
Confounding (Statistics)
Dihydrofolate reductase
Drug dosages
fatty liver
Liver cirrhosis
Liver diseases
Meta-analysis
Metabolic syndrome
Obesity
Patients
Psoriasis
Regression analysis
Review
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Summary:It has long been believed that methotrexate in therapeutic doses causes progressive liver injury resulting in advanced fibrosis and cirrhosis. Historically, this was a common indication for serial liver biopsy. However, new evidence suggests that methotrexate may not be a direct cause of liver injury; rather the injury and fibrosis attributed to methotrexate may be mediated by other mechanisms, specifically non-alcoholic fatty liver disease. The recent widespread use of non-invasive assessment of liver fibrosis has provided new evidence supporting this hypothesis. Thus, we conducted a meta-analysis and systematic review to determine whether methotrexate is indeed a direct cause of liver injury. For the meta-analysis portion, a comprehensive literature search was performed to identify manuscripts relevant to the topic. Of the 138 studies examined, 20 met our inclusion criteria. However, only 3 studies had sufficient homogeneity to allow aggregation. Thus, the remainder of the study was dedicated to a critical review of all studies relevant to the topic with particular attention to populations examined, risk factors, and assessment of injury and/or fibrosis. Meta-analysis did not show a statistically significant association between methotrexate dose and liver fibrosis. Individual studies reported fibrosis related to confounding factors such as diabetes, obesity, pre-existing chronic liver disease but not methotrexate exposure. In conclusion, existing evidence demonstrates that advanced liver fibrosis and cirrhosis previously attributed to methotrexate are in fact caused by metabolic liver disease or other chronic liver diseases, but not by methotrexate itself. This observation should direct the care of patients treated with long-term methotrexate.
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ISSN:1081-5589
1708-8267
DOI:10.1136/jim-2021-002206