{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:59:35Z","timestamp":1790632775199,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"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":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Compensated cirrhosis due to metabolic dysfunction\u2010associated steatotic liver disease (CC\u2010MASLD) increases morbidity and mortality risk but has no aetiology\u2010specific treatment. We investigated the safety and efficacy signals of severe energy restriction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this randomised controlled trial, adults with CC\u2010MASLD and obesity in a tertiary hepatology centre were randomised 2:1 to receive one\u2010to\u2010one remote dietetic support with a low\u2010energy (880\u2009kcal\/day, 80\u2009g protein\/day) total diet replacement programme for 12\u2009weeks and stepped food reintroduction for another 12\u2009weeks or standard of care (SoC). Given the exploratory nature of the study, three pre\u2010defined co\u2010primary outcomes were used to assess safety and efficacy signals: severe increases in liver biochemistry, changes in iron\u2010corrected T1, and changes in liver stiffness on magnetic resonance elastography. Changes in liver steatosis on magnetic resonance imaging, physical performance based on the physical performance test and liver frailty index, and changes in fat\u2010free mass were secondary outcomes. Magnetic resonance outcomes were assessed blind.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between February 2022 and September 2023, 17 participants (36% female, median [IQR] age 58 [7.5] years) were randomised to SoC (<jats:italic>n<\/jats:italic>\u2009=\u20096) or intervention (<jats:italic>n<\/jats:italic>\u2009=\u200911). The trial stopped earlier than planned due to slow recruitment rate. 91% and 94% of participants completed the intervention and attended the 24\u2010week follow\u2010up, respectively. Compared with the SoC, the between\u2010group weight change in the intervention was \u221211.9\u2009kg (95% CI: \u221217.2, \u22126.6, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) at 24\u2009weeks. Liver biochemistry markers (alanine transaminase, aspartate transaminase, and total bilirubin) were stable in everyone throughout the trial. Iron\u2010corrected T1 and steatosis significantly reduced (\u2212149.9\u2009ms [95% CI \u2212258.1, \u221241.7, <jats:italic>p<\/jats:italic>\u2009=\u20090.01] and \u22126% [95% CI \u221211.3, \u22120.6, <jats:italic>p<\/jats:italic>\u2009=\u20090.03], respectively). There were no between\u2010group differences in changes in liver stiffness (0.2\u2009kPa [95% CI \u22121.1, 1.6]), the physical performance test (1.5 points [95% CI \u22121.9 to 4.9], <jats:italic>p<\/jats:italic>\u2009=\u20090.70) or the liver frailty index (0 [95% CI \u22120.6 to 0.6], <jats:italic>p<\/jats:italic>\u2009=\u20090.97). Compared with SoC, absolute fat\u2010free mass reduced (\u22123.2\u2009kg [95% CI \u22126 to \u22120.3], <jats:italic>p<\/jats:italic>\u2009=\u20090.04) but relative fat\u2010free mass as percentage of total body weight increased (5.4% [95% CI 0.5 to 10.3], <jats:italic>p<\/jats:italic>\u2009=\u20090.046). No participant met the pre\u2010defined safety criteria for enhanced observation or intervention discontinuation. There was no between\u2010group differences in changes in cardiovascular markers and no evidence of hepatic decompensation or serious adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Severe energy restriction appears a safe option to achieve significant weight loss and reduce liver fat without adverse effects in people with CC\u2010MASLD. A larger study is needed to confirm these findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p>ISRCTN13053035, prospectively registered, overall study status: closed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13783","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T06:26:56Z","timestamp":1745562416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Severe Dietary Energy Restriction for Compensated Cirrhosis Due to Metabolic Dysfunction\u2010Associated Steatotic Liver Disease: A Randomised Controlled Trial"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1955-7234","authenticated-orcid":false,"given":"Dimitrios\u00a0A.","family":"Koutoukidis","sequence":"first","affiliation":[{"name":"Nuffield Department of Primary Care Health Sciences University of Oxford  Oxford UK"},{"name":"NIHR Oxford Biomedical Research Centre  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan\u00a0A.","family":"Jebb","sequence":"additional","affiliation":[{"name":"Nuffield Department of Primary Care Health Sciences University of Oxford  Oxford UK"},{"name":"NIHR Oxford Biomedical Research Centre  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy\u00a0W.","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"NIHR Oxford Biomedical Research Centre  Oxford UK"},{"name":"Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc\u00a0E.","family":"Mozes","sequence":"additional","affiliation":[{"name":"Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine University of Oxford  Oxford 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