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Here, we develop the MOFI-FL index, a simplified tool for HS detection, validate its performance against vibration-controlled transient elastography (VCTE), and evaluate its association with all-cause and cause-specific mortality. Using data from the Genetics of Atherosclerotic Disease study as our discovery cohort, we developed MOFI-FL, incorporating ALT, glucose, uric acid, and BMI, with computed tomography (CT) as the gold standard of HS. We used the continuous NHANES (2017\u20132018 cycles,<jats:italic> n<\/jats:italic>\u2009=\u20094,405) to validate against VCTE and compare our index with four previously validated HS indices (FLI, HSI, NAFLD-LFS, and AST\/ALT). Finally, we assessed all-cause and cause-specific mortality prediction using the NHANES-III cohort (<jats:italic>n<\/jats:italic>\u2009=\u200912,684) using Cox proportional hazards models adjusted for relevant confounders. The MOFI-FL index demonstrated good diagnostic performance in the internal validation cohort against CT (AUROC: 0.78 [95% CI: 0.72\u20130.83]; accuracy: 75% [70\u201379]) and against VCTE (NHANES 17\u201318: AUROC 0.77 [0.68\u20130.76]; accuracy: 70% [68\u201371]). It outperformed existing HS indices in the external cohort. Furthermore, a 1% increase in MOFI-FL was positively associated with all-cause mortality (HR\u2009=\u20091.005 [1.004\u20131.007]), as well as cardiovascular (HR\u2009=\u20091.008 [1.004\u20131.007]), diabetes-related (HR\u2009=\u20091.034 [1.028\u20131.040]), and nephrological deaths (HR\u2009=\u20091.012 [1.000\u20131.024]). MOFI-FL is a novel and simple tool for HS detection. It offers comparable performance to established indices and predictive capacity for cardiometabolic mortality, making it accessible for clinical and epidemiological applications.<\/jats:p>","DOI":"10.1038\/s41598-025-15487-7","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:53:33Z","timestamp":1755600813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-8198","authenticated-orcid":false,"given":"Juan","family":"Reyes-Barrera","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-3488","authenticated-orcid":false,"given":"Rosalinda","family":"Posadas-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-5163","authenticated-orcid":false,"given":"Gilberto","family":"Vargas-Alarc\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9525-1731","authenticated-orcid":false,"given":"Guillermo C.","family":"Cardoso-Salda\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9701-5879","authenticated-orcid":false,"given":"Paloma","family":"Almeda-Valdes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3093-937X","authenticated-orcid":false,"given":"Omar Yaxmehen","family":"Bello Chavolla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-1729","authenticated-orcid":false,"given":"Luis","family":"Ortiz-Hernandez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6879-1078","authenticated-orcid":false,"given":"Neftali Eduardo","family":"Antonio-Villa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"issue":"7","key":"15487_CR1","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/S2468-1253(21)00020-0","volume":"6","author":"G Targher","year":"2021","unstructured":"Targher, G., Tilg, H. & Byrne, C. 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