MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality

Abstract Hepatic steatosis (HS) is a common condition linked to increased cardiometabolic risk; however, biopsy and imaging-based methods limit the widespread diagnosis, especially in low-resource settings. Here, we develop the MOFI-FL index, a simplified tool for HS detection, validate its performa...

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Main Authors: Juan Reyes-Barrera, Rosalinda Posadas-Sánchez, Gilberto Vargas-Alarcón, Guillermo C. Cardoso-Saldaña, Paloma Almeda-Valdes, Omar Yaxmehen Bello Chavolla, Luis Ortiz-Hernandez, Neftali Eduardo Antonio-Villa
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Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-15487-7
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author Juan Reyes-Barrera
Rosalinda Posadas-Sánchez
Gilberto Vargas-Alarcón
Guillermo C. Cardoso-Saldaña
Paloma Almeda-Valdes
Omar Yaxmehen Bello Chavolla
Luis Ortiz-Hernandez
Neftali Eduardo Antonio-Villa
author_facet Juan Reyes-Barrera
Rosalinda Posadas-Sánchez
Gilberto Vargas-Alarcón
Guillermo C. Cardoso-Saldaña
Paloma Almeda-Valdes
Omar Yaxmehen Bello Chavolla
Luis Ortiz-Hernandez
Neftali Eduardo Antonio-Villa
author_sort Juan Reyes-Barrera
collection DOAJ
description Abstract Hepatic steatosis (HS) is a common condition linked to increased cardiometabolic risk; however, biopsy and imaging-based methods limit the widespread diagnosis, especially in low-resource settings. 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 (2017–2018 cycles, n = 4,405) 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 (n = 12,684) 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: 0.72–0.83]; accuracy: 75% [70–79]) and against VCTE (NHANES 17–18: AUROC 0.77 [0.68–0.76]; accuracy: 70% [68–71]). It outperformed existing HS indices in the external cohort. Furthermore, a 1% increase in MOFI-FL was positively associated with all-cause mortality (HR = 1.005 [1.004–1.007]), as well as cardiovascular (HR = 1.008 [1.004–1.007]), diabetes-related (HR = 1.034 [1.028–1.040]), and nephrological deaths (HR = 1.012 [1.000–1.024]). 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.
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spelling doaj-art-6aa4be1b47414d57a2a4e6b7c79195582025-08-24T11:30:36ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-15487-7MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortalityJuan Reyes-Barrera0Rosalinda Posadas-Sánchez1Gilberto Vargas-Alarcón2Guillermo C. Cardoso-Saldaña3Paloma Almeda-Valdes4Omar Yaxmehen Bello Chavolla5Luis Ortiz-Hernandez6Neftali Eduardo Antonio-Villa7Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma MetropolitanaDepartment of Endocrinology, Instituto Nacional de Cardiología Ignacio ChávezDepartment of Molecular Biology, Instituto Nacional de Cardiología Ignacio ChávezDepartment of Endocrinology, Instituto Nacional de Cardiología Ignacio ChávezEndocrinology and Metabolism Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránDivision of Research, Instituto Nacional de GeriatríaDepartamento de Atención a la Salud, Universidad Autónoma Metropolitana Unidad XochimilcoDepartment of Endocrinology, Instituto Nacional de Cardiología Ignacio ChávezAbstract Hepatic steatosis (HS) is a common condition linked to increased cardiometabolic risk; however, biopsy and imaging-based methods limit the widespread diagnosis, especially in low-resource settings. 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 (2017–2018 cycles, n = 4,405) 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 (n = 12,684) 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: 0.72–0.83]; accuracy: 75% [70–79]) and against VCTE (NHANES 17–18: AUROC 0.77 [0.68–0.76]; accuracy: 70% [68–71]). It outperformed existing HS indices in the external cohort. Furthermore, a 1% increase in MOFI-FL was positively associated with all-cause mortality (HR = 1.005 [1.004–1.007]), as well as cardiovascular (HR = 1.008 [1.004–1.007]), diabetes-related (HR = 1.034 [1.028–1.040]), and nephrological deaths (HR = 1.012 [1.000–1.024]). 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.https://doi.org/10.1038/s41598-025-15487-7Liver diseaseHepatic steatosisFatty liverClinical surrogate
spellingShingle Juan Reyes-Barrera
Rosalinda Posadas-Sánchez
Gilberto Vargas-Alarcón
Guillermo C. Cardoso-Saldaña
Paloma Almeda-Valdes
Omar Yaxmehen Bello Chavolla
Luis Ortiz-Hernandez
Neftali Eduardo Antonio-Villa
MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality
Scientific Reports
Liver disease
Hepatic steatosis
Fatty liver
Clinical surrogate
title MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality
title_full MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality
title_fullStr MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality
title_full_unstemmed MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality
title_short MOFI-FL, a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality
title_sort mofi fl a novel score for detecting hepatic steatosis and predicting cardiometabolic mortality
topic Liver disease
Hepatic steatosis
Fatty liver
Clinical surrogate
url https://doi.org/10.1038/s41598-025-15487-7
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