Liver function trends in children with suspected drug-induced hepatocellular injury: A survey using an electronic medical records database.

Background: Drug-induced liver injury (DILI) is a common adverse drug event with limited pediatric data in the literature. This study aimed to use pediatric electronic medical records to assess hepatocellular DILI in pediatric patients who were prescribed liver-injury-inducing drugs.

Methods: The Pediatric Medical Information Collection System (P-MICS) is a centralized database integrating electronic medical records from over 40 medical pediatric centers. Pediatric patients in the P-MICS with serum alanine aminotransferase (ALT) levels five or more times the upper limit of normal and who were below 15 years of age were selected. Those with liver diseases unrelated to drug-induced causes were excluded. We identified drugs prescribed 2 to 90 days before the first elevated ALT reading. High-risk liver-injury-causing drugs were determined based on the LiverTox score. We analyzed post-event ALT and total bilirubin levels (TB) and DILI management.

Results: Of the 817 patients with suspected DILI, 251 were prescribed four drugs identified as high-risk drugs for hepatocellular DILI: methotrexate (n = 129), aspirin (n = 82), vancomycin (n = 58), and cyclophosphamide (n = 51). The median ALT level at the first event was 245 U/L. Approximately 35% of methotrexate users and cyclophosphamide users experienced recurrent ALT elevation. Some methotrexate users also showed TB elevation. Discontinuation of high-risk drugs resulted in fewer relapses and TB elevations than pharmacotherapy.

Conclusions: The P-MICS effectively identifies pediatric patients with potential liver injury and tracks liver function in those prescribed liver-injury-causing drugs. This study underscores liver injury risks in pediatric anticancer drug users, highlighting the utility of the P-MICS in monitoring off-label drug safety in children.