Post hoc analyses
NAFLD, qSteatosis, steatosis, fibrosis
LIVER FIBROSIS, FIBROSIS, PROGRESSION, REGRESSION, STEATOSIS
Post hoc analyses included (1) assessment of histologic endpoints based on paired (baseline and week 48) review of biopsies, (2) AI-based digital quantitation of steatosis and liver fibrosis (qSteatosis and qFibrosis, respectively) in paired liver biopsies and (3) response rates at week 48 for relative HFF reduction by ≥30%. For analyzing the changes of liver fibrosis from baseline to week 48, based on the results from the paired reading by the central pathologist and from the AI-based digital quantitation (qFibrosis), patients in the placebo and both tropifexor arms were categorized as Progressor, No Change or Regressor (P/N/R analysis). The qFibrosis results were expressed both on a linear scale and by stage (F0 to F4) using an algorithm based on the blinded scoring of paired biopsies by the pathologist. For the conventional CRN scoring and for qFibrosis by stage, Progression was defined as fibrosis increase by ≥1 stage from baseline to week 48 and Regression was defined as fibrosis decrease by ≥1 stage. For qFibrosis on a linear scale, Progression was defined by increase ≥1 s.e.m. and Regression was defined as decrease of ≥1 s.e.m., based on the qFibrosis algorithm. The s.e.m. was determined when developing the qFibrosis algorithm using a cohort of 200 patients with the full spectrum of NAFLD, which included 42 patients with F2 and 57 patients with F3 stage of fibrosis. The s.e.m. for each fibrosis stage, as determined from the algorithm development, was then applied as a predetermined cut-off in qFibrosis assessment on a continuous scale in all subsequent studies (including the present one). The s.e.m. numerical values for F2 and F3 were 0.09 and 0.086, respectively.