Acute Transient Aminotransferase Elevation is Common With Intrathecal Methotrexate, but Liver Injury is Infrequent
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".