Evaluating the Sensitivity and Specificity of Promising Circulating Biomarkers to Diagnose Liver Injury in Humans

Abstract Early diagnosis of drug-induced liver injury (DILI) continues to be a major hurdle during drug development and postmarketing. The objective this study was evaluate the diagnostic performance promising biomarkers injury—glutamate dehydrogenase (GLDH), cytokeratin-18 (K18), caspase-cleaved K18 (ccK18), osteopontin (OPN), macrophage colony-stimulating factor (MCSF), MCSF receptor (MCSFR), microRNA-122 (miR-122) in comparison traditional biomarker alanine aminotransferase (ALT). Biomarkers were evaluated individually as multivariate model cohort acetaminophen overdose (n = 175) subjects further tested cohorts healthy adults 135), patients with damage from various causes 104), muscle 74), kidney 40), gastrointestinal tract 37), pancreas 34). In cohort, GLDH, K18, miR-122 able detect DILI more accurately than individual alone. Furthermore, three-biomarker could predict compared volunteers or muscle, pancreas, tract, kidney. Expression using database transcriptomic profiles across multiple tissues/organs humans rats. mRNA (Krt18) MiR-122 highly expressed whereas GLDH (Glud1) widely expressed. We performed comprehensive, comparative assessment 7 demonstrated that 3-biomarker can injury.