{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:12:35Z","timestamp":1779905555118,"version":"3.53.1"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Advanced liver fibrosis (ALF) predicts an adverse prognosis in chronic liver disease. In addition to etiological treatment, a new approach to stop or reverse residual fibrosis is desirable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the efficacy and safety of prolonged\u2010release pirfenidone (PR\u2010PFD) versus placebo in compensated cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>180 patients with ALF (F4) were randomly assigned to: placebo, 1200 mg\/d, and 1800\u2009mg\/d PR\u2010PFD, plus standardised care, for 24mo. Frequency of lab tests: (3mo), liver stiffness measurement (LSM), FibroTest, ultrasound (US) (6mo), and endoscopy (annually).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fibrosis evolution estimated from LSM was significantly lower only in the 1200 compared to placebo and 1800 groups (24.2\u2009\u00b1\u20092.4 vs. 15.4\u2009\u00b1\u20092.4; 27.6\u2009\u00b1\u20092.4 vs. 24.6\u2009\u00b1\u20092.4; 24.4\u2009\u00b1\u20092.3 vs. 23.3\u2009\u00b1\u20092.3\u2009kPa, respectively, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), in intergroup analysis, meeting the primary endpoint. Fibrotest was significantly lower only in the 1200\u2009mg\/d group, compared to baseline values (0.86\u2009\u00b1\u20090.02 vs. 0.83\u2009\u00b1\u20090.02\u2009units, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Liver function test (LFT's) also improved as well as Model for End\u2010Stage Liver Disease (MELD) score and quality of life (QoL). Decompensations occurred in 19 patients: 12 ascites (more frequent in placebo, <jats:italic>p<\/jats:italic>\u2009=\u20090.003), 5 variceal bleeding, 4 encephalopathies, 4 hepatocarcinomas. Adverse events were mainly mild gastrointestinal (<jats:italic>n<\/jats:italic>\u2009=\u200935, 48 and 46, <jats:italic>p<\/jats:italic>\u2009=\u20090.010) and cutaneous (<jats:italic>n<\/jats:italic>\u2009=\u200912, 15, and 22, <jats:italic>p<\/jats:italic>\u2009=\u20090.0001) in placebo, 1200 and 1800\u2009mg\/day, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PR\u2010PFD at a dose of 1200\u2009mg significantly decreased non\u2010invasive liver fibrosis markers at 24\u2009months and induced improvement in LFT's, MELD, and QoL in compensated cirrhosis, without safety concerns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov identifier: NCT01046474<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.70131","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T13:58:35Z","timestamp":1747922315000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Noninvasive Evaluation of Prolonged\u2010Release Pirfenidone in Compensated Liver Cirrhosis. <scp>ODISEA<\/scp> Study, a Randomised Trial"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0455-9325","authenticated-orcid":false,"given":"Linda E.","family":"Mu\u00f1oz\u2010Espinosa","sequence":"first","affiliation":[{"name":"Universidad Aut\u00f3noma de Nuevo Le\u00f3n, \u201cDr. Jos\u00e9 E. Gonz\u00e1lez\u201d University Hospital  Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Torre","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cisneros","sequence":"additional","affiliation":[{"name":"Christus Muguerza Hospital  Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iaarah","family":"Montalvo","sequence":"additional","affiliation":[{"name":"Liver Clinic  M\u00e9rida Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Mal\u00e9","sequence":"additional","affiliation":[{"name":"Digestive and Hepatic Disease Institute  Guadalajara Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scherezada","family":"Mej\u00eda","sequence":"additional","affiliation":[{"name":"Juarez Hospital  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Ram\u00f3n","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Mexican Group for the Study of Liver Diseases (PROMHEPA)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Lizardi","sequence":"additional","affiliation":[{"name":"Mexican Group for the Study of Liver Diseases (PROMHEPA)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Zu\u00f1iga\u2010Noriega","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Nuevo Le\u00f3n, \u201cDr. Jos\u00e9 E. 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