Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design

•Population-derived estimates of progression risk are essential in estimating the sample size for interventional trials in NAFLD.•Among adults with compensated NASH cirrhosis, the risk of progression to decompensation or death is 10% per year.•Among adults with first decompensation, the risk of progression to subsequent liver events of death is 32% per year.•Trials in compensated cirrhosis would require at least 2,886 participants followed for ≥2 years to detect a ≥15% relative decrease in liver-related endpoints.