Tu1009 Assessing the Utility of Adult Drug Induced Liver Injury Criteria in the Pediatric Patient: A Pilot Analysis

in the US and described in LiverTox (http://livertox.nih.gov) were classified into five categories: A: ≥50 published cases, B: <50 but ≥12, C: <12 but ≥4, D: 1-3, E: none.All case reports in the C and D category were reanalyzed by two independent reviewers using the Roussel Uclaf Causality Assessment Method (RUCAM).Drugs with case reports of fatality due to DILI and those documenting a positive rechallenge were noted.Herbal and dietary supplements (HDS) were excluded.DILI considered due to direct hepatotoxicity was not included in the analysis.Results: Overall 563 drugs were described in LiverTox, but 31 were HDS leaving 531 drugs for analysis.A total of 51 drugs had ≥50 published case reports of DILI, 49 of which (94%) included at least one fatal case; the exceptions being fenofibrate and oral contraceptives.Overall 80 drugs were in category B, 39 (49%) with a fatal case and 26/80 (33%) with rechallenge.Among drugs in category C, 146 upon review included at least one convincing published case report, 19 (13%) including a fatal instance and 32 (22%) had a positive rechallenge.Category D included 89 drugs, 3 (3%) with a fatality, and 14 (16%) with rechallenge cases.The remaining 165 drugs had no convincing published cases of hepatotoxicity although 94 had initially been placed in categories C or D. However, the evidence for hepatotoxicity was either not published or was insufficiently documented to be scored as either possible or probable by RUCAM.In contrast, among the drugs in category C and D 962 of 1225 published case reports could be classified as either possible or probable by the RUCAM method.Conclusions: There is a large variety in the documentation of hepatoxicity among drugs implicated in DILI.The vast majority of drugs with well documented hepatotoxicity have been associated with fatal outcome.The hepatotoxicity of many drugs listed as causing DILI has not been documented in the published literature.The frequency of published data on DILI associated with drugs and rechallenge should play an important role in the causality assessment of drugs suspected of DILI.