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©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2026; 18(2): 113743
Published online Feb 27, 2026. doi: 10.4254/wjh.v18.i2.113743
Published online Feb 27, 2026. doi: 10.4254/wjh.v18.i2.113743
Should the theory of methotrexate-induced liver toxicity be abandoned?
Yahya Al-Hammada, Sinan Sharba, Sahlgrenska Academy, University of Gothenburg, Gothenburg 41345, Vastra Gotaland, Sweden
Samer Al-Dury, School of Public Health and Community Medicine, University of Gothenburg, Gothenburg 40530, Sweden
Samer Al-Dury, Department of Gastroenterology, Medical City Hospital for Military and Security Services, Muscat 111, Oman
Samer Al-Dury, Department of Gastroenterology and Hepatology, University Hospital Ghent, Gent 9000, Flanders, Belgium
Author contributions: Al-Hammada Y contributed to literature review and consolidation; Sharba S and Al-Dury S participated in the manuscript writing and revision; Al-Dury S contributed to study conceptualization and design. All authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Samer Al-Dury, MD, PhD, School of Public Health and Community Medicine, University of Gothenburg, Universitetsplatsen 1, Gothenburg 40530, Sweden.
Received: September 10, 2025
Revised: October 21, 2025
Accepted: December 16, 2025
Published online: February 27, 2026
Processing time: 163 Days and 20.2 Hours
Revised: October 21, 2025
Accepted: December 16, 2025
Published online: February 27, 2026
Processing time: 163 Days and 20.2 Hours
Core Tip
Core Tip: Methotrexate (MTX) has long been associated with a presumed risk of hepatotoxicity and progressive liver fibrosis, largely based on early biopsy-era studies. Contemporary evidence using non-invasive fibrosis assessment shows that significant fibrosis is uncommon in MTX-treated patients and more strongly linked to metabolic dysfunction-associated steatotic liver disease and related risk factors such as obesity, diabetes, and insulin resistance. This minireview challenges the traditional perception of intrinsic MTX hepatotoxicity and argues for risk-based rather than drug-based monitoring strategies.