ArticleLiver international : official journal of the International Association for the Study of the Liver2025
Acute Transient Aminotransferase Elevation is Common With Intrathecal Methotrexate, but Liver Injury is Infrequent.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Acute Lymphoblastic Leukemia Presenting With Initial Hyperbilirubinemia and Significantly Elevated Liver Transaminases: A Rare Pediatric Case With Unadjusted Chemotherapy.Clinical medicine insights. Case reports · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
BACKGROUND AND
aimsHepatotoxicity is a known risk of oral and intravenous methotrexate (MTX), but whether intrathecal (IT) administration causes hepatotoxicity remains unknown. We aimed to explore whether IT-MTX causes acute hepatoxicity.
methodsRetrospective single-centre analysis of all patients treated with IT-MTX from 2000 to 2020. We compared liver enzymes (LE) at baseline (within 7 days before IT-MTX) to post-MTX (within 7 days after IT-MTX). LE elevation was defined as ≥ 50% increase in LE from baseline and greater than upper limit of normal. Drug-induced liver injury (DILI) was defined based on established criteria.
resultsA total of 270 patients (184 adults and 86 paediatric) received IT-MTX and had available LE data. Aminotransferase elevation was seen post-MTX in 107 (40%) patients, of whom 96 (36%) had ALT and 68 (25%) had AST elevation. DILI occurred in 16 (6%) patients. Aminotransferases peaked a median of 4 (3-5) days post-MTX, returning near baseline by day 7. Paediatric patients had higher incidence of aminotransferase elevations and DILI than adults (ALT 51% vs. 28%; AST 41% vs. 18%; DILI 11% vs. 3%; p < 0.01 for all). No significant predictors of LE elevation or DILI were identified, and no patient developed liver failure. The severity of ALT elevation after the first IT-MTX dose did not predict severity of a subsequent dose.
conclusionAcute transient aminotransferase elevation is common after IT-MTX, especially in paediatric patients. Only a fraction of patients developed DILI, which was self-limited with no sensitisation or liver failure.
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