{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T21:08:55Z","timestamp":1784581735315,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":215,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Canadian Journal of Gastroenterology and Hepatology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p><jats:italic>Introduction<\/jats:italic>. Acute\u2010on\u2010chronic liver failure (ACLF) is an acute liver decompensation in cirrhotic patients, which leads to organ failures and high short\u2010term mortality. The treatment is based on the management of complications and, in severe cases, liver transplantation. Since specific treatment is unavailable, we aimed to evaluate the safety and initial efficacy of bone marrow mesenchymal stem cells (BM\u2010MSC) in patients with ACLF Grades 2 and 3, a population excluded from previous clinical trials. <jats:italic>Methods<\/jats:italic>. This is a randomized placebo\u2010controlled phase I\u2010II single center study, which enrolled 9 cirrhotic patients from 2018 to 2020, regardless of the etiology. The control group (<jats:italic>n<\/jats:italic>\u2009=\u20095) was treated with standard medical therapy (SMT) and placebo infusion of saline. The intervention group (<jats:italic>n<\/jats:italic>\u2009=\u20094) received SMT plus 5 infusions of 1\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> cells\/kg of BM\u2010MSC for 3 weeks. Both groups were monitored for 90 days. A Chi\u2010square test was used for qualitative variables, and the <jats:italic>t<\/jats:italic>\u2010test and Mann\u2013Whitney <jats:italic>U<\/jats:italic> test for quantitative variables. The Kaplan\u2013Meier estimator was used to build survival curves. In this study, we followed the intention\u2010to\u2010treat analysis, with a significance of 5%. <jats:italic>Results<\/jats:italic>. Nine patients with a mean Child\u2013Pugh (CP) of 12.3, MELD of 38.4, and CLIF\u2010C score of 50.7 were recruited. Hepatitis C and alcohol were the main etiologies. The average infusion per patient was 2.9 and only 3 patients (2 in control and 1 in the BM\u2010MSC group) received all the protocol infusions. There were no infusion\u2010related side effects, although one patient in the intervention group presented hypernatremia and a gastric ulcer, after the third and fifth infusions, respectively. The survival rate after 90 days was 20% (1\/5) for placebo versus 25% (1\/4) for the BM\u2010MSC. The patient who completed the entire MSC protocol showed a significant improvement in CP (C\u201014 to B\u20109), MELD (32 to 22), and ACLF (grade 3 to 0). <jats:italic>Conclusion<\/jats:italic>. BM\u2010MSC infusion is safe and feasible in patients with ACLF Grades 2 and 3.<\/jats:p>","DOI":"10.1155\/2021\/3662776","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T19:21:13Z","timestamp":1628104873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Bone Marrow Mesenchymal Stem Cells in Acute\u2010on\u2010Chronic Liver Failure Grades 2 and 3: A Phase I\u2010II Randomized Clinical Trial"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6991-1174","authenticated-orcid":false,"given":"Fernando Comunello","family":"Schacher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelise","family":"Martins Pezzi da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia Mariano da 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