RT Journal Article T1 Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis. A1 Sanyal, Arun J A1 Anstee, Quentin M A1 Trauner, Michael A1 Lawitz, Eric J A1 Abdelmalek, Manal F A1 Ding, Dora A1 Han, Ling A1 Jia, Catherine A1 Huss, Ryan S A1 Chung, Chuhan A1 Wong, Vincent Wai-Sun A1 Okanoue, Takeshi A1 Romero-Gomez, Manuel A1 Muir, Andrew J A1 Afdhal, Nezam H A1 Bosch, Jaime A1 Goodman, Zachary A1 Harrison, Stephen A A1 Younossi, Zobair M A1 Myers, Robert P AB Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver-related complications in patients with NASH cirrhosis. Patients with compensated cirrhosis due to NASH were enrolled in two placebo-controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH Clinical Research Network (CRN) and Ishak classifications and a machine learning (ML) approach, hepatic collagen and alpha-smooth muscle actin (α-SMA) expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (enhanced liver fibrosis [ELF], NAFLD fibrosis score [NFS], and Fibrosis-4 index [FIB-4]) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver-related clinical events. Among 1,135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow-up of 16.6 months, 71 (6.3%) had a liver-related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, α-SMA expression, ML-based fibrosis parameters, LS, ELF, NFS, and FIB-4. Cirrhosis regression observed in 16% (176/1,135) between BL and W48 was associated with a lower risk of events versus nonregression (1.1% [2/176] vs. 7.2% [69/957]; HR, 0.16; 95% CI, 0.04, 0.65 [p = 0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, α-SMA, ML-based fibrosis parameters, NFS, and LS were associated with an increased risk of events. In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver-related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis. YR 2022 FD 2022-02-07 LK http://hdl.handle.net/10668/21984 UL http://hdl.handle.net/10668/21984 LA en DS RISalud RD Feb 14, 2025