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

Area of Science:

• Neurology
• Hepatology
• Pharmacology

Background:

• Hepatotoxicity is a known risk of systemic methotrexate (MTX).
• The potential for hepatotoxicity from intrathecal methotrexate (IT-MTX) administration is not well-established.
• This study investigates acute liver injury following IT-MTX.

Purpose of the Study:

• To determine if intrathecal methotrexate (IT-MTX) causes acute hepatotoxicity.
• To analyze the incidence and characteristics of liver enzyme elevations and drug-induced liver injury (DILI) after IT-MTX.

Main Methods:

• Retrospective analysis of 270 patients receiving IT-MTX from 2000-2020.
• Comparison of liver enzymes (LE) before and within 7 days after IT-MTX administration.
• Definition of LE elevation and DILI based on established criteria.

Main Results:

• 40% of patients experienced aminotransferase elevation post-IT-MTX.
• Drug-induced liver injury (DILI) occurred in 6% of patients.
• Paediatric patients showed a higher incidence of aminotransferase elevations and DILI compared to adults.

Conclusions:

• Acute, transient aminotransferase elevations are frequent after IT-MTX, especially in pediatric patients.
• Drug-induced liver injury (DILI) is uncommon, self-limiting, and does not lead to sensitization or liver failure.
• No significant predictors for LE elevation or DILI were identified.