Is There A Future For NAFLD/NASH Trials Without Biopsies?

By Mark Tengowski, DVM, MS, PhD – Director, Medical & Scientific Affairs at Clario

The liver, nestled within the abdominal cavity, is a remarkable entity. It operates as a metabolic dynamo, undertaking the essential tasks of transforming, storing, detoxifying, and synthesizing vital substances. Gaining insight into non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) necessitates familiarity with the diagnostic criteria, which entails examining liver tissue biopsies processed, stained, and evaluated using liver hematoxylin and eosin (H&E) histology by a proficient (hepato)pathologist.

According to the current perspective of the FDA, the diagnosis and assessment of NAFLD/NASH can be achieved solely through liver biopsy and the subsequent interpretation of histological findings (as stated in the Draft Guidance of December 2018 and June 2019). The FDA supports the use of noninvasive imaging biomarkers, which can replace liver biopsies in liver studies, provided the sponsor proposes diagnostic criteria that have not been established for patient selection or efficacy assessment.

For non-cirrhotic and non-alcoholic fatty liver with fibrosis, the FDA advises using histological improvements as endpoints to predict clinical benefit, even considering the invasiveness and logistical challenges of liver biopsies in clinical trials. What can noninvasive imaging tell us about these cellular events?

Explore the possibilities of conducting trials for NAFLD and NASH without having to rely on invasive biopsies.