Preclinical safety assessment: current gaps, challenges, and approaches in identifying translatable biomarkers of drug-induced liver injury.

Currently, no serum biomarkers, including the biochemical gold standard alanine aminotransferase, can differentiate drug-induced from non-drug-related liver injury, can differentiate liver injury mediated by a specific drug or mechanism, or can accurately predict the progression and outcome of hepatic injury. Efforts have been made by veterinary clinical pathologists, toxicologists, and other scientists to address the gaps in hepatic biomarkers faced during drug development; although there have been no breakthroughs, several novel biomarker candidates have been identified. Efforts to address the gaps in translatable hepatic biomarkers and the challenges and hurdles faced during this process are highlighted in this review.