Publication:
Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis.

dc.contributor.authorSanyal, Arun J
dc.contributor.authorAnstee, Quentin M
dc.contributor.authorTrauner, Michael
dc.contributor.authorLawitz, Eric J
dc.contributor.authorAbdelmalek, Manal F
dc.contributor.authorDing, Dora
dc.contributor.authorHan, Ling
dc.contributor.authorJia, Catherine
dc.contributor.authorHuss, Ryan S
dc.contributor.authorChung, Chuhan
dc.contributor.authorWong, Vincent Wai-Sun
dc.contributor.authorOkanoue, Takeshi
dc.contributor.authorRomero-Gomez, Manuel
dc.contributor.authorMuir, Andrew J
dc.contributor.authorAfdhal, Nezam H
dc.contributor.authorBosch, Jaime
dc.contributor.authorGoodman, Zachary
dc.contributor.authorHarrison, Stephen A
dc.contributor.authorYounossi, Zobair M
dc.contributor.authorMyers, Robert P
dc.date.accessioned2023-05-03T14:44:16Z
dc.date.available2023-05-03T14:44:16Z
dc.date.issued2022-02-07
dc.description.abstractSurrogate 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.doi10.1002/hep.32204
dc.identifier.essn1527-3350
dc.identifier.pmcPMC9303958
dc.identifier.pmid34662449
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303958/pdf
dc.identifier.unpaywallURLhttps://boris.unibe.ch/162222/1/hep.32204.pdf
dc.identifier.urihttp://hdl.handle.net/10668/21984
dc.issue.number5
dc.journal.titleHepatology (Baltimore, Md.)
dc.journal.titleabbreviationHepatology
dc.language.isoen
dc.organizationHospital Universitario Virgen del Rocío
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.page.number1235-1246
dc.pubmedtypeControlled Clinical Trial
dc.pubmedtypeJournal Article
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.meshCollagen
dc.subject.meshFibrosis
dc.subject.meshHumans
dc.subject.meshLiver
dc.subject.meshLiver Cirrhosis
dc.subject.meshNon-alcoholic Fatty Liver Disease
dc.titleCirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number75
dspace.entity.typePublication

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