Antimicrobials and anti-epileptics are the leading causes of idiosyncratic drug induced liver injury in american children.

Abstract

OBJECTIVES\nTo 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.\n\n\nMETHODS\nConsecutive definite, highly likely, or probable cases in children enrolled into the ongoing DILIN prospective and retrospective studies between 9/04 and 2/17 were reviewed.\n\n\nRESULTS\n57 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\u200aU/L (33-4185), alkaline phosphatase 203\u200aU/L (62-1177), and total bilirubin 3.3\u200amg/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\u200a=\u200a11) and valproate (n\u200a=\u200a6). 63% 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.\n\n\nCONCLUSIONS\nAntimicrobials (51%) and antiepileptic drugs (21%) are the most frequently implicated agents in pediatric DILI patients. While the majority of cases are self-limited, there is potential for serious morbidity including acute liver failure, chronic liver injury, and death.