January 28, 2022
Causality assessment for suspected drug-induced liver injury (DILI) is a major challenge during drug development and becomes a greater challenge when studies are done in patients with NASH who typically enter the trial already with liver blood test elevations.
Whether or not to obtain a liver biopsy to aid in diagnosis of suspected DILI is a subject of ongoing debate. The inherent risks of a liver biopsy must be weighed against the potential useful information to be obtained from evaluation of liver tissue. Histologic results may be nonspecific and have little impact in establishing the diagnosis of DILI or in changing the clinical assessment; however, histologic evaluation of liver tissue is the only way to characterize the pattern, severity, and distribution of hepatic injury, and may have prognostic value.
Prior to considering a liver biopsy, other issues must be addressed, such as the extent and nature of blood tests to obtain, the phase of drug development, and the issue of rechallenge. Also, consideration as to the establishment of an external DILI monitoring committee prior to study start, were discussed.