Noninvasive Quantification of Hepatic Steatosis Using Ultrasound-Derived Fat Fraction (CHESS2303): A Prospective Multicenter Study

Abstract

Ultrasound-derived fat fraction (UDFF) is designed to assess the hepatic fat content quantitatively. A multicenter study that verifies the diagnostic performance of UDFF for detecting hepatic steatosis has not yet been reported. This study aimed to evaluate the performance of UDFF for diagnosing and grading hepatic steatosis. Participants referred for assessment of hepatic steatosis were prospectively recruited from eight hospitals. All participants underwent UDFF and magnetic resonance imaging proton density fat fraction (MRI-PDFF) examinations. MRI-PDFF was used as the reference for diagnosing hepatic steatosis. From January 2023 to July 2023, a total of 300 participants were included. The median body mass index was 25.4 kg/m² (interquartile range: 22.7–28.1). UDFF values were positively correlated with MRI-PDFF (R = 0.80, p < 0.001). Using MRI-PDFF ≥ 5%, ≥ 15%, and ≥ 25% as the reference standard for detecting mild, moderate, and severe hepatic steatosis, the best cutoff values of UDFF were 7.6% (area under the receiver operating characteristic curves [AUC] = 0.90), 15.9% (AUC = 0.90), and 22.3% (AUC = 0.91), respectively. Thus, UDFF has excellent diagnostic performance in detecting and grading hepatic steatosis.

Keywords

hepatic steatosis / magnetic resonance imaging proton density fat fraction (MRI-PDFF) / noninvasive / quantification / ultrasound-derived fat fraction (UDFF)

References

[1] M. E. Rinella, J. V. Lazarus, V. Ratziu, et al., “A Multisociety Delphi Consensus Statement on New Fatty Liver Disease Nomenclature,” Journal of Hepatology 79, no. 6 (2023): 1542–1556.

[2] V. W. Wong, M. Ekstedt, G. L. Wong, and H. Hagström, “Changing Epidemiology, Global Trends and Implications for Outcomes of NAFLD,” Journal of Hepatology 79, no. 3 (2023): 842–852.

[3] P. Pitisuttithum and S. Treeprasertsuk, “Nonalcoholic Fatty Liver Disease (NAFLD) Among Older Adults,” Portal Hypertension & Cirrhosis 1, no. 3 (2022): 184–191.

[4] L. Miao, G. Targher, C. D. Byrne, L. Valenti, X. Qi, and M.-H. Zheng, “Portal Hypertension in Nonalcoholic Fatty Liver Disease: Challenges and Perspectives,” Portal Hypertension & Cirrhosis 1, no. 1 (2022): 57–65.

[5] H. Guo, H. Ni, J. Xue, et al., “Global Scientific Trends on Portal Hypertension and Cirrhosis in the 21st Century: A Bibliometric and Visualized Analysis,” Portal Hypertension & Cirrhosis 2, no. 1 (2023): 46–48.

[6] G. Ferraioli, A. Berzigotti, R. G. Barr, et al., “Quantification of Liver Fat Content With Ultrasound: A WFUMB Position Paper,” Ultrasound in Medicine & Biology 47, no. 10 (2021): 2803–2820.

[7] A. Tang, A. Desai, G. Hamilton, et al., “Accuracy of MR Imaging-estimated Proton Density Fat Fraction for Classification of Dichotomized Histologic Steatosis Grades in Nonalcoholic Fatty Liver Disease,” Radiology 274, no. 2 (2015): 416–425.

[8] K. A. Wear, A. Han, J. M. Rubin, et al., “US Backscatter for Liver Fat Quantification: An AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative,” Radiology 305, no. 3 (2022): 526–537.

[9] D. Petroff, V. Blank, P. N. Newsome, et al., “Assessment of Hepatic Steatosis by Controlled Attenuation Parameter Using the M and XL Probes: An Individual Patient Data Meta-analysis,” The Lancet Gastroenterology and Hepatology 6, no. 3 (2021): 185–198.

[10] EASL Clinical Practice Guidelines on Non-Invasive Tests for Evaluation of Liver Disease Severity and Prognosis-2021 Update. Journal of Hepatology 2021; 75(3): 659–689.

[11] M. E. Rinella, B. A Neuschwander-Tetri, M. S. Siddiqui, et al., “AASLD Practice Guidance on the Clinical Assessment and Management of Nonalcoholic Fatty Liver Disease,” Hepatology 77, no. 5 (2023): 1797–1835.

[12] D. T. Fetzer, I. M Rosado-Mendez, M. Wang, et al., “Pulse-Echo Quantitative US Biomarkers for Liver Steatosis: Toward Technical Standardization,” Radiology 305, no. 2 (2022): 265–276.

[13] R. De Robertis, F. Spoto, D. Autelitano, et al., “Ultrasound-derived Fat Fraction for Detection of Hepatic Steatosis and Quantification of Liver Fat Content,” La radiologia Medica 128, no. 10 (2023): 1174–1180.

[14] Y. Labyed and A. Milkowski, “Novel Method for Ultrasound-Derived Fat Fraction Using an Integrated Phantom,” Journal of Ultrasound in Medicine 39, no. 12 (2020): 2427–2438.

[15] F. Tavaglione, V. Flagiello, F. Terracciani, et al., “Non-Invasive Assessment of Hepatic Steatosis by Ultrasound-derived Fat Fraction in Individuals at High-risk for Metabolic Dysfunction-associated Steatotic Liver Disease,” Diabetes Metabolism Research and Reviews 40, no. 3 (2024): e3787.

[16] J. R. Dillman, S. Thapaliya, J. A. Tkach, and A. T. Trout, “Quantification of Hepatic Steatosis by Ultrasound: Prospective Comparison With MRI Proton Density Fat Fraction as Reference Standard,” Ajr American Journal of Roentgenology 219, no. 5 (2022): 784–791.

[17] M. Recalde, A. Pistillo, V. Davila-Batista, et al., “Longitudinal Body Mass Index and Cancer Risk: A Cohort Study of 2.6 Million Catalan Adults,” Nature Communications 14, no. 1 (2023): 3816.

[18] N. Chalasani, Z. Younossi, J. E. Lavine, et al., “The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance From the American Association for the Study of Liver Diseases,” Hepatology 67, no. 1 (2018): 328–357.

[19] G. Ferraioli, R. G. Barr, A. Berzigotti, et al., “WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification,” Ultrasound in Medicine & Biology 50, no. 8 (2024): 1088–1098.

[20] G. Ferraioli, V. Kumar, A. Ozturk, K. Nam, C. L. de Korte, and R. G. Barr, “US Attenuation for Liver Fat Quantification: An AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative,” Radiology 302, no. 3 (2022): 495–506.

[21] Y. L. Huang, J. Cheng, Y. Wang, et al., “Hepatic Steatosis Using Ultrasound-Derived Fat Fraction: First Technical and Clinical Evaluation,” Clinical Hemorheology and Microcirculation 86, no. 1-2 (2024): 51–61.

[22] G. Ferraioli, A. Raimondi, L. Maiocchi, et al., “Liver Fat Quantification With Ultrasound: Depth Dependence of Attenuation Coefficient,” Journal of Ultrasound in Medicine 42, no. 10 (2023): 2247–2255.

[23] J. Gao, C. Wong, M. Maar, and D. Park, “Reliability of Performing Ultrasound Derived SWE and Fat Fraction in Adult Livers,” Clinical Imaging 80 (2021): 424–429.

[24] S. D. Serai, J. R. Dillman, and A. T. Trout, “Proton Density Fat Fraction Measurements at 1.5-and 3-T Hepatic MR Imaging: Same-Day Agreement Among Readers and Across Two Imager Manufacturers,” Radiology 284, no. 1 (2017): 244–254.

[25] EASL Clinical Practice Guidelines: Management of Alcohol-related Liver Disease. Journal of Hepatology 2018; 69(1): 154–181.

[26] T. Yokoo, S. D. Serai, A. Pirasteh, et al., “Linearity, Bias, and Precision of Hepatic Proton Density Fat Fraction Measurements by Using MR Imaging: A Meta-Analysis,” Radiology 286, no. 2 (2018): 486–498.

[27] T. Yokoo, M. Shiehmorteza, G. Hamilton, et al., “Estimation of Hepatic Proton-Density Fat Fraction by Using MR Imaging at 3.0 T,” Radiology 258, no. 3 (2011): 749–759.

[28] A. Tang, J. Tan, M. Sun, et al., “Nonalcoholic Fatty Liver Disease: MR Imaging of Liver Proton Density Fat Fraction to Assess Hepatic Steatosis,” Radiology 267, no. 2 (2013): 422–431.

[29] Y. Mise, S. Satou, J. Shindoh, et al., “Three-dimensional Volumetry in 107 Normal Livers Reveals Clinically Relevant Inter-Segment Variation in Size,” HPB (Oxford) 16, no. 5 (2014): 439–447.

[30] J. Starekova, D. Hernando, P. J. Pickhardt, and S. B. Reeder, “Quantification of Liver Fat Content With CT and MRI: State of the Art,” Radiology 301, no. 2 (2021): 250–262.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.