Does methotrexate cause liver fibrosis? — Donovan Hair Clinic

Methotrexate is an immunosuppressant used for treating many immune based hair loss conditions including alopecia areata, lichen planopilaris, frontal fibrosing alopecia, discoid lupus and scalp dermatomyositis.

For many years, one of the feared complications of methotrexate (MTX) use has been the possible development of liver fibrosis. Data is slowly accumulating that questions whether the drug itself is actually responsible for fibrosis or whether underlying underlying health issues in the patient like obesity, diabetes, alcohol use, age, and metabolic syndrome are really the key factors associated with fibrosis. It seems that the latter may be the more likely answer.

A meta-analysis by Conway et al of 32 randomized controlled trials of MTX vs. comparator in adults with RA, psoriasis and inflammatory bowel disease indicated that exposure to MTX was not associated with risk of liver failure, cirrhosis, or death (relative risk 0.12; 95% CI 0.01–1.09).

A recent review by Cheema and colleagues concluded that advanced liver fibrosis and cirrhosis previously attributed to methotrexate are in fact more likely to be caused caused by metabolic liver disease or other chronic liver diseases, but not by methotrexate itself. In their recent review, the authors proposed that studies in the past that did report fibrosis were complicated by confounding factors such as diabetes, obesity, pre-existing chronic liver disease but not methotrexate exposure.

All in all, it appears methotrexate use may not be the key factor driving fibrosis. Instead, it may the underlying metabolic syndrome and issues related to underlying non alcoholic fatty liver disease that are the key factors in the development of fibrosis.


Conway R, Low C, Coughlan RJ, O’Donnell MJ, Carey JJ. Risk of liver injury among methotrexate users: a meta-analysis of randomised controlled trials. Semin Arthritis Rheum 2015;45(2):156–162

Cheema HI et al. Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis. J Investig Med. 2022 Oct;70(7):1452-1460.


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