Volume 151, Issue 6, Pages 1046-1051 (December 2016) Drug-Induced Liver Injury in Patients With Preexisting Chronic Liver Disease in Drug Development: How to Identify and Manage?  Naga Chalasani  Gastroenterology  Volume 151, Issue 6, Pages 1046-1051 (December 2016) DOI: 10.1053/j.gastro.2016.10.010 Copyright © 2016 AGA Institute Terms and Conditions

Figure 1 An eDISH plot in patients with normal liver tests at baseline. eDISH plot showing peak ALT and TBL levels from a database of a phase III clinical trial. The peak serum ALT is shown along the x-axis, and the peak serum TBL is shown along the y-axis as multiples of the ULN on log scales. Over-representation of points on the study drug in the Hy’s law range quadrant and the Temple’s corollary range quadrant suggests a possible increased risk of severe DILI. ALT, alanine aminotransferase; DILI, drug-induced liver injury; eDISH, Evaluation of Drug-Induced Serious Hepatotoxicity; TBL, total bilirubin; ULN, upper limit of normal. Gastroenterology 2016 151, 1046-1051DOI: (10.1053/j.gastro.2016.10.010) Copyright © 2016 AGA Institute Terms and Conditions

Figure 2 A proposed modification to the eDISH plot for patients with metastatic liver disease. A modified eDISH plot showing peak ALT and TBL levels as multiples of the baseline values. The 4 quadrants are defined by a line corresponding with 5× the baseline ALT and a line corresponding with 2× baseline TBL. Over representation of points on the study drug in the right upper quadrant and the right lower quadrant suggests a possible increased risk of DILI. ALT, alanine aminotransferase; DILI, drug-induced liver injury; eDISH, Evaluation of Drug-Induced Serious Hepatotoxicity; TBL, total bilirubin; ULN, upper limit of normal. Gastroenterology 2016 151, 1046-1051DOI: (10.1053/j.gastro.2016.10.010) Copyright © 2016 AGA Institute Terms and Conditions