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This study aimed to evaluate the efficacy and safety of atorvastatin in preventing recurrent decompensation events (DDs) and in modulating the gut\u2013liver axis among patients with decompensated cirrhosis. In this randomized, double -blind, placebo-controlled trial, 100 adults with decompensated cirrhosis were randomly assigned in a 1:1 ratio to receive either atorvastatin (20\u00a0mg\/day) or placebo for six months. The primary endpoint was the incidence of recurrent decompensation events (DDs). Secondary outcomes included changes in biomarkers of oxidative stress (malondialdehyde [MDA]), systemic inflammation (nuclear factor kappa B [NF-\u03baB], C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]), intestinal permeability (zonulin), and endotoxemia (lipopolysaccharide [LPS]). Atorvastatin treatment significantly reduced the cumulative recurrence of cirrhosis-related complications compared to placebo (36% vs. 72%; HR 0.50; 95% CI, 0.33\u20130.75;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Notably, atorvastatin conferred complete protection against hepatorenal syndrome (HRS) (0% vs. 20% in the placebo group; all Type 2). These clinical improvements were mirrored by significant reductions in MDA, NF-\u03baB, LPS, and zonulin levels (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05), indicating a robust attenuation of systemic inflammation and restoration of intestinal barrier integrity. Atorvastatin was well-tolerated; while mild myalgia was more frequent in the intervention group (14% vs. 2%), elevations in transaminases were transient and clinically insignificant. In this randomized trial, atorvastatin was associated with a lower recurrence of decompensation events and a reduced incidence of hepatorenal syndrome compared with placebo. These effects were accompanied by improvements in biomarkers related to systemic inflammation and gut\u2013liver axis dysfunction. Atorvastatin was generally well tolerated, although mild myalgia occurred more frequently and warrants clinical monitoring. While these findings suggest a potential role for atorvastatin as an adjunctive therapy in decompensated cirrhosis, confirmation in larger, multicenter studies is required before broader clinical application.\n                    <jats:bold>Clinical trial number<\/jats:bold>\n                    : NCT05563389 (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/register.clinicaltrials.gov\/prs\/beta\/studies\/S000CHKM00000052\/recordSummary\" ext-link-type=\"uri\">https:\/\/register.clinicaltrials.gov\/prs\/beta\/studies\/S000CHKM00000052\/recordSummary<\/jats:ext-link>\n                    ).\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-41326-4","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T08:54:54Z","timestamp":1774083294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Atorvastatin reduces recurrent decompensation events in advanced cirrhosis in a randomized placebo-controlled trial"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-5236","authenticated-orcid":false,"given":"Khadija A.M.","family":"Glal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0882-7315","authenticated-orcid":false,"given":"Sahar M.","family":"El-Haggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4366-2218","authenticated-orcid":false,"given":"Sherief M.","family":"Abdel-Salam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1071-5416","authenticated-orcid":false,"given":"Tarek M.","family":"Mostafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"key":"41326_CR1","unstructured":"Cirrhosis of the Liver: What is It, Symptoms, Causes & Stages. 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The protocol for this work was assessed and approved by the Research Ethics Committee (internal review board) at Tanta University (13\/6\/2022). The study procedure was planned to follow the ethical guidelines of the 1975 Declaration of Helsinki. Written informed consent was obtained from all participants before inclusion in the study. Trial results will be disseminated through publication in a peer-reviewed journal and presentation at scientific meetings. A summary of the results will be made available on the ClinicalTrials.gov registry.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent for publication was obtained from all participants. All authors have reviewed and approved the final version of the manuscript and consent to its publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"9669"}}