Drug-Induced Injury of Liver, Heart, Kidney, and Skin: Employing Recent Advances to Improve Patient Safety and Speed Up the Pipeline

Causality assessment for suspected DILI is a major challenge in clinical practice and during drug development. In contrast to many other liver disorders, there is currently no specific biomarker or a combination of tests that will establish the diagnosis of DILI and differentiate it from other causes of liver injury. DILI may resemble almost any type of liver disease, and the clinicopathologic spectrum may range from nonspecific injury, to acute and chronic hepatitis, granulomatous liver disease, cholestasis, fatty infiltration, vascular lesions, and hepatic tumors.

The diagnosis of DILI is therefore virtually always presumptive, as it is based on clinical assessment and exclusion of other possible causes rather than on absolute criteria and specific diagnostic tests. Abnormal liver tests may be caused by numerous liver disorders as well as extra-hepatic disorders, many of which are considerably more common than typical DILI. It is therefore critical to exclude other liver diseases before attributing a liver injury to a drug. Exclusion of other causes requires detailed information pertaining to the patient’s clinical course and laboratory data. Failure to test for other causes may result in assigning guilt by association which may often be erroneous.

This session will address three topics pertaining to causality assessment during drug development. The first session will focus on common pitfalls and potential solutions, the second session will address causality assessment in patients with underlying hepatitis B and C, and the third session will address the use of the Roussel Uclaf Causality Assessment Method (RUCAM) versus expert opinion for causality assessment during drug development.