Proton density fat fraction for diagnosis of metabolic dysfunction-associated steatotic liver disease

Nikolaos Panagiotopoulos¹, Tanya Wolfson², David T Harris¹, Danielle Batakis³, Rashmi Agni⁴, Lael Ceriani³, Yesenia Covarrubias³, Gavin Hamilton³, Michael S Middleton³, Vitor F Martins³, Anthony C Gamst^{2

5}, Thekla H Oechtering¹, Ryan Sappenfield⁴, Santiago Horgan⁶, Eduardo Grunvald⁷, Luke M Funk^{8

9}, Garth R Jacobsen⁶, Anne O Lidor⁸, James A Goodman¹⁰, Sami B Khoury³, Claude B Sirlin³, Scott B Reeder^{1

11

12

13

14}

Affiliations

¹ Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
² Computational and Applied Statistical Laboratory (CASL), San Diego Supercomputer Center, University of California San Diego, San Diego, California, USA.
³ Department of Radiology, University of California San Diego, San Diego, California, USA.
⁴ Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁵ Department of Mathematics, University of California San Diego, San Diego, California, USA.
⁶ Department of Surgery, University of California San Diego, San Diego, California, USA.
⁷ Department of Medicine, University of California San Diego, San Diego, California, USA.
⁸ Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁹ Department of Surgery. William S. Middleton VA, Madison, Wisconsin, USA.
¹⁰ Translational Clinical Sciences, Pfizer Research & Development, Cambridge, Massachusetts, USA.
¹¹ Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹² Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹³ Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹⁴ Department of Emergency Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

PMID: 40132140
PMCID: PMC12353623 (available on 2026-03-25)
DOI: 10.1097/HEP.0000000000001318

Proton density fat fraction for diagnosis of metabolic dysfunction-associated steatotic liver disease

Nikolaos Panagiotopoulos et al. Hepatology. 2025.

. 2025 Mar 25:10.1097/HEP.0000000000001318.

doi: 10.1097/HEP.0000000000001318. Online ahead of print.

Authors

Affiliations

¹ Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
² Computational and Applied Statistical Laboratory (CASL), San Diego Supercomputer Center, University of California San Diego, San Diego, California, USA.
³ Department of Radiology, University of California San Diego, San Diego, California, USA.
⁴ Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁵ Department of Mathematics, University of California San Diego, San Diego, California, USA.
⁶ Department of Surgery, University of California San Diego, San Diego, California, USA.
⁷ Department of Medicine, University of California San Diego, San Diego, California, USA.
⁸ Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁹ Department of Surgery. William S. Middleton VA, Madison, Wisconsin, USA.
¹⁰ Translational Clinical Sciences, Pfizer Research & Development, Cambridge, Massachusetts, USA.
¹¹ Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹² Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹³ Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹⁴ Department of Emergency Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.

PMID: 40132140
PMCID: PMC12353623 (available on 2026-03-25)
DOI: 10.1097/HEP.0000000000001318

Abstract

Background and aims: Prior work has shown that MRI-derived proton density fat fraction (PDFF) can diagnose metabolic dysfunction-associated steatotic liver disease (MASLD) noninvasively, but there is a paucity of data on the performance of PDFF to classify more advanced forms of the MASLD spectrum. The purpose of this study was to assess the diagnostic performance of PDFF for the diagnoses of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), and fibrotic MASH in adults with obesity undergoing bariatric surgery, using contemporaneous intraoperative liver biopsy as a reference.

Approach and results: PDFF was evaluated alone and with other potential classifiers (imaging, serum and anthropometric), using Bayesian Information Criterion-based stepwise logistic regression models. Areas under the receiver operating characteristic (ROC) curves (AUC) were computed for all models and single classifiers. Cross-validated sensitivity and specificity were calculated at Youden-based PDFF classification thresholds. Data analysis from 140 patients demonstrated that PDFF was the most accurate single classifier, with high AUC for MASLD (0.95), MASH (0.85), and fibrotic MASH (0.82) (all p <0.001). Multivariable models, including PDFF, outperformed those without PDFF. The Youden-based threshold for PDFF was 4.4% for MASLD (sensitivity: 87%, specificity: 86%), 6.9% for MASH (sensitivity: 77%, specificity: 66%), and 13.5% for fibrotic MASH (sensitivity: 67%, specificity: 85%).

Conclusions: PDFF was the most accurate single classifier for diagnosing MASLD, MASH, and fibrotic MASH. The most accurate multivariable classification models for MASLD, MASH, and fibrotic MASH included PDFF, demonstrating the central importance of PDFF for noninvasive assessment of the MASLD spectrum.

Keywords: MASLD; PDFF; magnetic resonance imaging (MRI); metabolic dysfunction–associated steatohepatitis (MASH); quantitative imaging biomarker.

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Conflict of interest statement

Michael S. Middleton consults for, advises, received grants from, has other interests with, owns stock in, and is employed by Livivos. He consults for, advises, has other interests with, and is employed by AutonomUS. He consults for, advises, and is employed by PharmaNest. He received grants from and owns stock in Pfizer. He owns stock in and is employed by Quantix Bio. Santiago Horgan consults for and is employed by Stryker. He consults for Ethicon. Eduardo Grunvald consults for and received grants from Novo Nordisk. He advises B2M Medical. Luke M. Funk received grants from the Veterans Health Administration. He has other interests with Wolters Kluwer. Garth R. Jacobsen consults for W.L. Gore and Intuitive Surgical. James A. Goodman owns stock in and is employed by Pfizer. Claude B. Sirlin consults for, advises, and owns stock in Livivos. He consults for and received grants from Pfizer, Ascelia, and Pharma AB. He received grants from and has other interests with University of Cincinnati and Sociedad Radiológica de Puerto Rico. He consults for AMRA, Boehringer, Exact Sciences, Altimmune, Blade, Epigenomics, and Guerbet. He received grants from ACR, Bayer, Butterfly, GE, Gilead, Philips, Siemens, V Foundation, OrsoBio, Enanta, Gilead, ICON, Intercept, Nusirt, Shire, Synageva, Takeda, Fundacion, Santa Fe Congreso Argentino de Diagnóstico por Imágenes, Stanford Jornada Paulista de Radiologia, RSNA, Hospital Español Auxilio Mutuo Puerto Rico, and Paris MASH Liver Forum. He has other interests with Medscape, Wolters Kluwer, and HealthProMatch Educational symposia. The remaining authors have no conflicts to report.

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Proton density fat fraction for diagnosis of metabolic dysfunction-associated steatotic liver disease

Affiliations

Proton density fat fraction for diagnosis of metabolic dysfunction-associated steatotic liver disease

Authors

Affiliations

Abstract

Conflict of interest statement

References

Grants and funding

LinkOut - more resources

Full Text Sources