Methotrexate (MTX) is a widely used, cost-effective systemic treatment for moderate-to-severe psoriasis, but concerns about hepatotoxicity often limit its long-term use. Hepatic adverse effects range from transient enzyme elevations to fibrosis and cirrhosis. Despite established guidelines, monitoring practices remain inconsistent, and the mechanisms underlying MTX-induced hepatotoxicity in psoriasis patients are not fully elucidated. This systematic literature review evaluates the association between MTX and hepatotoxicity, identifies key risk factors, assesses monitoring strategies and addresses misconceptions about its hepatic safety. A comprehensive search of MEDLINE/PubMed, EMBASE, Cochrane Library and grey literature (2003-2024) included English and French studies on human subjects, encompassing guidelines, reviews and observational/interventional studies. MTX-related hepatotoxicity is multifactorial, with risk factors including obesity, diabetes, hyperlipidaemia, excessive alcohol consumption and pre-existing liver disease. Psoriasis itself may also contribute to liver dysfunction. There is no consensus on optimal monitoring frequency for liver function tests or the role of noninvasive tools like transient elastography. While folic acid supplementation may mitigate risk, dosing remains inconsistent.Though MTX carries a potential hepatotoxic risk, this is patient-specific rather than inherent to the drug. Standardized monitoring protocols and risk stratification are essential to optimize safety, prevent unnecessary treatment discontinuation and improve long-term psoriasis management.
