Publication: Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis.
dc.contributor.author | Sanyal, Arun J | |
dc.contributor.author | Anstee, Quentin M | |
dc.contributor.author | Trauner, Michael | |
dc.contributor.author | Lawitz, Eric J | |
dc.contributor.author | Abdelmalek, Manal F | |
dc.contributor.author | Ding, Dora | |
dc.contributor.author | Han, Ling | |
dc.contributor.author | Jia, Catherine | |
dc.contributor.author | Huss, Ryan S | |
dc.contributor.author | Chung, Chuhan | |
dc.contributor.author | Wong, Vincent Wai-Sun | |
dc.contributor.author | Okanoue, Takeshi | |
dc.contributor.author | Romero-Gomez, Manuel | |
dc.contributor.author | Muir, Andrew J | |
dc.contributor.author | Afdhal, Nezam H | |
dc.contributor.author | Bosch, Jaime | |
dc.contributor.author | Goodman, Zachary | |
dc.contributor.author | Harrison, Stephen A | |
dc.contributor.author | Younossi, Zobair M | |
dc.contributor.author | Myers, Robert P | |
dc.date.accessioned | 2023-05-03T14:44:16Z | |
dc.date.available | 2023-05-03T14:44:16Z | |
dc.date.issued | 2022-02-07 | |
dc.description.abstract | 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. | |
dc.identifier.doi | 10.1002/hep.32204 | |
dc.identifier.essn | 1527-3350 | |
dc.identifier.pmc | PMC9303958 | |
dc.identifier.pmid | 34662449 | |
dc.identifier.pubmedURL | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303958/pdf | |
dc.identifier.unpaywallURL | https://boris.unibe.ch/162222/1/hep.32204.pdf | |
dc.identifier.uri | http://hdl.handle.net/10668/21984 | |
dc.issue.number | 5 | |
dc.journal.title | Hepatology (Baltimore, Md.) | |
dc.journal.titleabbreviation | Hepatology | |
dc.language.iso | en | |
dc.organization | Hospital Universitario Virgen del Rocío | |
dc.organization | Instituto de Biomedicina de Sevilla-IBIS | |
dc.page.number | 1235-1246 | |
dc.pubmedtype | Controlled Clinical Trial | |
dc.pubmedtype | Journal Article | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.accessRights | open access | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject.mesh | Collagen | |
dc.subject.mesh | Fibrosis | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Liver | |
dc.subject.mesh | Liver Cirrhosis | |
dc.subject.mesh | Non-alcoholic Fatty Liver Disease | |
dc.title | Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis. | |
dc.type | research article | |
dc.type.hasVersion | VoR | |
dc.volume.number | 75 | |
dspace.entity.type | Publication |
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