Antimicrobials and Antiepileptics Are the Leading Causes of Idiosyncratic Drug‐induced Liver Injury in American Children

Abstract

Objectives: The aim of this study was to provide an overview of the presenting features, etiologies, and outcomes of children enrolled in the Drug‐induced Liver Injury Network (DILIN) prospective and retrospective studies. Methods: Consecutive definite, highly likely, or probable cases in children enrolled into the ongoing DILIN prospective and retrospective studies between September 2004 and February 2017 were reviewed. Results: Fifty‐seven cases were adjudicated as definite (14), highly likely (30), or probable (13) DILI. Median age was 14.3 years (1.7–17.9), 67% female, and 82% Caucasian. At DILI onset, 82% had hepatocellular injury with a median alanine aminotransferase of 411 U/L (33–4185), alkaline phosphatase 203 U/L (62–1177), and total bilirubin 3.3 mg/dL (0.2–33.9). The median duration of suspect medication use was 55 days (1–2789) and the most frequently implicated individual agents were minocycline (n = 11) and valproate (n = 6). Sixty‐three percent were hospitalized and 3 (5%) underwent liver transplant within 1 month of DILI onset. Among 46 children followed for at least 6 months, 8 (17%) met criteria for chronic DILI with 6 of them having persistent liver injury at 24 months of follow‐up. A genome‐wide association study in 39 Caucasian children focusing on regions associated with pediatric cholestatic liver disease failed to demonstrate any single nucleotide polymorphism associated with DILI susceptibility or outcome. Conclusions: Antimicrobials (51%) and antiepileptic drugs (21%) are the most frequently implicated agents in pediatric DILI patients. Although the majority of cases are self‐limited, there is potential for serious morbidity including acute liver failure, chronic liver injury, and death.