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 411U/L (33-4185), alkaline phosphatase 203U/L (62-1177), and total bilirubin 3.3mg/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.