RESUMEN
BACKGROUND: The FDA provides guidance regarding pre-marketing liver chemistry subject stopping criteria. This study was undertaken to determine the background rates of liver chemistry abnormalities in pediatric clinical trials for conditions with and without underlying liver disease (LD). METHODS: The study included 5410 subjects aged 0-18years in 24 trials for conditions without LD. 3756 pediatric subjects in 14 trials for conditions with LD (malaria, HIV, HBV) were also analyzed. Prevalence and incidence of abnormal liver chemistries were calculated. RESULTS: In conditions without LD, the overall incidence were 0.54 (95%CI 0.20-1.17) per 1000 person-months for ALT⩾3xULN, 0.36 (95%CI 0.10-0.92) for ALT⩾5xULN, and 0.27 (95%CI 0.06-0.78) for ALT⩾8xULN, 1.03 (95%CI 0.50-1.90) for ALP⩾2xULN, and 0.22 (95%CI 0.03-0.78) for combined ALT⩾3xULN and TBIL⩾2xULN. Incidence of ALT⩾3xULN (8.17 95%CI 6.42-10.24) were much higher in trials of conditions with LD. However, combined elevations of ALT⩾3xULN and TBIL⩾2xULN were only marginally higher 0.37 (95%CI 0.10-1.08). CONCLUSION: Elevations of ALT (3xULN) and TBIL (2xULN) are rare in pediatric trial populations for conditions without underlying liver disease and can be considered a safety signal. For trials in conditions with liver disease, the potential for drug-induced liver injury must be distinguished from underlying disease progression.