AUTHOR=Wang Yang , Li Yimin , Liu Yun , Zhang Yifan , Ke Ziliang , Zhang Yu , Liu Yulan 

TITLE=Patients With IBD Receiving Methotrexate Are at Higher Risk of Liver Injury Compared With Patients With Non-IBD Diseases: A Meta-Analysis and Systematic Review

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.774824

DOI=10.3389/fmed.2021.774824

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Methotrexate is well-known in treating inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis (Ps), and psoriatic arthritis (PsA). Several reports have indicated a higher incidence of methotrexate (MTX)-related liver adverse events in patients with IBD. We aim to investigate the risk of liver injury in patients with IBD and those with non-IBD diseases treated with MTX.</p><p><bold>Methods:</bold> We searched PubMed, Embase, and the Cochrane Library for articles that reported liver adverse events in patients with IBD, RA, and Ps/PsA, receiving MTX therapy. Additional articles were obtained by screening the references of recent meta-analysis and reviews. Raw data from included articles were pooled to calculate the cumulative incidence of total liver injury (TLI), MTX discontinuation (MTX-D), and liver fibrosis (LF). RR (relative risk) was calculated to compare the difference between patients with IBD and those with non-IBD diseases.</p><p><bold>Results:</bold> A total of 326 articles with 128,876 patients were included. The patients with IBD had higher incidence of TLI [11.2 vs. 9.2%; relative risk (RR) = 1.22; <italic>P</italic> = 0.224] and MTX-D (2.6 vs. 1.8%; RR, 1.48; <italic>P</italic> = 0.089) than patients with non-IBD diseases. Due to the publication bias, trim-and-fill was performed. Afterwards, the patients with IBD showed significantly higher risk of TLI (11.2 vs. 3%; RR = 3.76; <italic>p</italic> &lt; 0.001), MTX-D (3.3 vs. 0.7%; RR = 5; <italic>p</italic> &lt; 0.001) and LF (3.1 vs. 0.1%; RR = 38.62; <italic>P</italic> = 0.001) compared with patients with non-IBD diseases.</p><p><bold>Conclusion:</bold> IBD is associated with a higher risk of MTX-related liver injury. The mechanism of MTX-induced hepatotoxicity might be different in IBD and non-IBD diseases, and needs to be verified in future research.</p>