Acute Transient Aminotransferase Elevation is Common With Intrathecal Methotrexate, but Liver Injury is Infrequent

IF 5.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2025-02-10 DOI:10.1111/liv.70022

Harish Gopalakrishna, Julian Hercun, Nirali N. Shah, Mark Roschewski, Yaron Rotman

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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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急性一过性转氨酶升高是常见的鞘内甲氨蝶呤，但肝损伤是罕见的

背景和目的甲氨蝶呤（MTX）的肝毒性是已知的口服和静脉注射的风险，但是鞘内给药（IT）是否会引起肝毒性仍然未知。我们的目的是探讨IT-MTX是否会引起急性肝毒性。方法回顾性分析2000年至2020年所有接受IT-MTX治疗的患者。我们比较了基线（IT-MTX治疗前7天内）和治疗后（IT-MTX治疗后7天内）的肝酶（LE）。LE升高定义为LE较基线增加≥50%且大于正常上限。药物性肝损伤（DILI）是根据既定标准定义的。结果共有270例患者（184例成人和86例儿科）接受了IT-MTX治疗，并获得了LE数据。mtx治疗后，107例（40%）患者出现转氨酶升高，其中96例（36%）有ALT， 68例（25%）有AST升高。DILI发生在16例（6%）患者中。转氨酶在甲氨蝶呤治疗后4（3-5）天达到峰值，到第7天恢复到接近基线水平。儿童患者的转氨酶升高和DILI发生率高于成人(ALT 51% vs. 28%；AST 41% vs. 18%；DILI 11% vs. 3%；P < 0.01)。没有发现明显的LE升高或DILI的预测因素，也没有患者发生肝功能衰竭。第一次给药后ALT升高的严重程度不能预测后续给药的严重程度。结论IT-MTX术后急性一过性转氨酶升高是常见的，尤其是在儿科患者中。只有一小部分患者发展为DILI，这是自限性的，没有致敏或肝衰竭。

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.