The Association of Histologic and Non-invasive Tests with Adverse Clinical and Patient-Reported Outcomes in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis (NASH).

Abstract Background and Aim Fibrosis is an independent predictor of death in NASH. We assessed the associations between histologic and non-invasive (NITs) fibrosis tests with clinical and patient-reported outcomes (PROs) in advanced NASH. Methods Patients with advanced NASH (NASH CRN stage F3 or F4) were enrolled in four multinational clinical trials of simtuzumab and selonsertib. Liver biopsies, NITs, and PROs (SF-36, CLDQ-NASH, EQ-5D, WPAI) were prospectively collected. Results 2154 patients with advanced NASH were included: 52.5% F4, 40% male, 72% type 2 diabetes, baseline liver stiffness 24.1±14.2 kPa in F4, 14.6 ± 8.0 kPa in F3, baseline mean ELF score 11.4±1.2 in F4, 10.3±1.0 in F3; median follow-up16 months. Of those with baseline F3, 16.7% experienced disease progression to cirrhosis while those with F4, 7.3% experienced clinical events (39% ascites, 24% hepatic encephalopathy); patients who progressed had higher baseline NITs (all p Conclusions Baseline NIT scores and their changes over time are predictors of adverse clinical and PROs in patients with advanced NASH.