{"doi":"10.1111/liv.70022","title":"Acute Transient Aminotransferase Elevation is Common With Intrathecal Methotrexate, but Liver Injury is Infrequent","abstract":"BACKGROUND AND AIMS: Hepatotoxicity 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. METHODS: Retrospective 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. RESULTS: A 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. CONCLUSION: Acute 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.","journal":"Liver International","year":2025,"id":550153,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9267,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":502790,"name":"Julian Hercun","orcid":"0000-0001-7608-0914","position":1,"is_corresponding":false},{"id":280941,"name":"Nirali N. Shah","orcid":"0000-0002-8474-9080","position":2,"is_corresponding":false},{"id":233601,"name":"Mark Roschewski","orcid":"0000-0003-0278-2635","position":3,"is_corresponding":false},{"id":231169,"name":"Yaron Rotman","orcid":"0000-0002-7549-8216","position":4,"is_corresponding":false},{"id":1107755,"name":"Harish Gopalakrishna","orcid":"0000-0003-3175-4983","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:54:12.321988Z","pmid":"39927416","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}