1 Stanford University.
2 Saint Louis University.
3 National Cancer Institute.
4 Bundesinstitut für Arzneimittel und Medizinprodukte/ European Medicines Agency.
5 Northwestern University.
6 Pinnacle Clinical Research.
7 Hospital Pitié-Salpêtrière.
8 Virginia Commonwealth University.
9 University of California, San Diego.
10 Summit Clinical Research.
11 Novo Nordisk, Denmark.
12 University of California, Berkeley.
Identifying effective therapies for nonalcoholic steatohepatitis (NASH) with fibrosis is a pressing challenge, with 1-2% of the population in developed nations at risk of developing NASH cirrhosis and its complications. The design of NASH clinical therapeutic trials is hampered by the long period of minimally symptomatic disease that typically precedes the development of decompensated cirrhosis, and the accompanying uncertainties regarding the best pre-cirrhotic trial endpoints that reliably reflect a subsequent reduction in liver-related morbidity and mortality. The Liver Forum is a multi-stakeholder organization comprised of academic, industry, and regulatory experts working from a regulatory science perspective to identify barriers, prioritize research, and identify solutions to accelerate therapeutic development for NASH. Prior work of The Liver Forum has focused on recommendations for disease definitions and baseline parameters to be implemented in clinical trials that are designed to assess disease status and prevent progression to cirrhosis, liver transplantation, hepatocellular carcinoma, and death. The purpose of this summary is to review currently available clinical data to identify parameters that change in parallel with liver histology and are likely to reflect clinically meaningful reductions in the risk of developing cirrhosis and its complications. We review available data on exploratory histologic, blood-based and imaging pharmacodynamic biomarkers that may reflect meaningful treatment responses and provide recommendations regarding measurements to be considered in phase 2 and 3 trials as well as during post-marketing monitoring trials.