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 Wai-Sun-Wong, Vincent
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
K1 Collagen
K1 Humans
K1 Liver Cirrhosis
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.
PB Wolters Kluwer Health
YR 2022
FD 2022
LK http://hdl.handle.net/10668/21984
UL http://hdl.handle.net/10668/21984
LA en
NO Sanyal AJ, Anstee QM, Trauner M, Lawitz EJ, Abdelmalek MF, Ding D, et al. Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis. Hepatology. 2022 May;75(5):1235-1246.
DS RISalud
RD Jul 3, 2025