US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study

Katsutoshi Sugimoto; Fuminori Moriyasu; Marco Dioguardi Burgio; Valérie Vilgrain; Daniel Jesper; Deike Strobel; Valentin Blank; Thomas Karlas; Edward G. Grant; Linda C. Kelahan; Helena Gabriel; Byung Ihn Choi; Takashi Nishimura; Hiroko Iijima; Theodore J. Dubinsky; Jing Gao; Dong Ho Lee; Jae Young Lee; Yanan Zhao; Pintong Huang; Jie Zeng; Adrian Lim; Xiaoyan Xie; Richard G. Barr; Vito Cantisani; Giovanna Ferraioli; Kentaro Sakamaki; Takao Itoi; Masayoshi Kage; Hirohisa Yano

doi:10.1148/radiol.233377

US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study

Katsutoshi Sugimoto^*, Fuminori Moriyasu, Marco Dioguardi Burgio, Valérie Vilgrain, Daniel Jesper, Deike Strobel, Valentin Blank, Thomas Karlas, Edward G. Grant, Linda C. Kelahan, Helena Gabriel, Byung Ihn Choi, Takashi Nishimura, Hiroko Iijima, Theodore J. Dubinsky, Jing Gao, Dong Ho Lee, Jae Young Lee, Yanan Zhao, Pintong HuangJie Zeng, Adrian Lim, Xiaoyan Xie, Richard G. Barr, Vito Cantisani, Giovanna Ferraioli, Kentaro Sakamaki, Takao Itoi, Masayoshi Kage, Hirohisa Yano

^*Corresponding author for this work

Radiology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Background: Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose: To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods: This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results: A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion: Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation.

Original language	English (US)
Article number	e233377
Journal	Radiology
Volume	312
Issue number	2
DOIs	https://doi.org/10.1148/radiol.233377
State	Published - Aug 2024

Funding

Disclosures of conflicts of interest: K. Sugimoto No relevant relationships. F.M. Institution has a research contract from Canon Medical Systems to evaluate a new function of the Canon US machine; institution receives grants and rents US equipment from Canon Medical Systems; director of Medilec, which has a consulting contract and receives honoraria for consulting on this study, workshops, conference presentations, manuscript submission and publishing; travel expenses from Canon Medical Systems. M.D.B. Payment for presentation from Canon Medical Systems. V.V. No relevant relationships. D.J. No relevant relationships. D.S. No relevant relationships. V.B. No relevant relationships. T.K. Financial support to institution for conducting the study, provision of software for the US system, and travel expenses for study meeting from Canon Medical Systems; provision of material (FibroScan) for clinical studies on related topics from Echosens; payment or honoraria for lectures and speaking from Jazz Pharmaceuticals and Echosens; participation on a clinical advisory board for Echosens; speaker of the Sonography Working Group of the German Society for Gastroenterology, Digestive and Metabolic Diseases; head of the Internal Medicine Section of the German Society of Ultrasound in Medicine. E.G.G. Multicentered grant to institution from Canon Medical Systems and grants or contracts from Siemens Healthineers; consultant for Radiology. L.C.K. No relevant relationships. H.G. On the board of the Society of Radiologists in Ultrasound and chair of the American College of Radiology US Guidelines Committee. B.I.C. No relevant relationships. T.N. No relevant relationships. H.I. Research grants from Canon Medical Systems and GE HealthCare. T.J.D. No relevant relationships. J.G. Clinical research funding and US scanner loan to institution to support this study from Canon Medical Systems; principal investigator on this study funded by Canon Medical Systems; honorarium for lecture from RSNA. D.H.L. Research grant from Canon Medical Systems. J.Y.L. Korean national grants for the development of histotripsy and brain device; Focused Ultrasound Foundation grants for clinical research of high-intensity focused ultrasound; vice president of Asian Federation of Societies for Ultrasound in Medicine and Biology; board member of the International Society for Therapeutic Ultrasound; stock options from the International Immunogenetics Information System. Y.Z. No relevant relationships. P.H. No relevant relationships. J.Z. No relevant relationships. A.L. Payment for speakers bureau and loan of equipment from Canon Medical Systems. X.X. No relevant relationships. R.G.B. No relevant relationships. V.C. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bracco, Canon, Siemens, Samsung, and Mindray; support for attending meetings and/or travel from Bracco, Esaote, Samsung, Siemens, Canon, and Mindray; president elect of the European Federation for Ultrasound in Medicine and Biology; past president of the Societ\u00E0 Italiana di Ultrasonologia in Medicina e Biologia; and US section chairman of the Italian Society of Medical and Interventional Radiology. G.F. Grants or contracts to institution from Canon Medical Systems, Esaote, Fujifilm Medical Systems, and Siemens Healthineers; royalties or licenses from Elsevier; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Canon Medical Systems, Fujifilm Healthcare, Mindray Medical Imaging, Philips Ultrasound, and Siemens Healthineers; participation on a data and safety monitoring board or advisory board for Philips Healthcare; and equipment received by institution from Canon Medical Systems, Esaote, and Fujifilm Medical Systems. K. Sakamaki No relevant relationships. T.I. No relevant relationships. M.K. No relevant relationships. H.Y. No relevant relationships.

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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10.1148/radiol.233377

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Sugimoto, K., Moriyasu, F., Burgio, M. D., Vilgrain, V., Jesper, D., Strobel, D., Blank, V., Karlas, T., Grant, E. G., Kelahan, L. C., Gabriel, H., Choi, B. I., Nishimura, T., Iijima, H., Dubinsky, T. J., Gao, J., Lee, D. H., Lee, J. Y., Zhao, Y., ... Yano, H. (2024). US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study. Radiology, 312(2), Article e233377. https://doi.org/10.1148/radiol.233377

@article{c56599e4fca547499e87e0d54b437a76,

title = "US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study",

abstract = "Background: Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose: To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods: This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results: A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion: Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation.",

author = "Katsutoshi Sugimoto and Fuminori Moriyasu and Burgio, {Marco Dioguardi} and Val{\'e}rie Vilgrain and Daniel Jesper and Deike Strobel and Valentin Blank and Thomas Karlas and Grant, {Edward G.} and Kelahan, {Linda C.} and Helena Gabriel and Choi, {Byung Ihn} and Takashi Nishimura and Hiroko Iijima and Dubinsky, {Theodore J.} and Jing Gao and Lee, {Dong Ho} and Lee, {Jae Young} and Yanan Zhao and Pintong Huang and Jie Zeng and Adrian Lim and Xiaoyan Xie and Barr, {Richard G.} and Vito Cantisani and Giovanna Ferraioli and Kentaro Sakamaki and Takao Itoi and Masayoshi Kage and Hirohisa Yano",

year = "2024",

month = aug,

doi = "10.1148/radiol.233377",

language = "English (US)",

volume = "312",

journal = "Radiology",

issn = "0033-8419",

publisher = "Radiological Society of North America Inc.",

number = "2",

}

Sugimoto, K, Moriyasu, F, Burgio, MD, Vilgrain, V, Jesper, D, Strobel, D, Blank, V, Karlas, T, Grant, EG, Kelahan, LC , Gabriel, H, Choi, BI, Nishimura, T, Iijima, H, Dubinsky, TJ, Gao, J, Lee, DH, Lee, JY, Zhao, Y, Huang, P, Zeng, J, Lim, A, Xie, X, Barr, RG, Cantisani, V, Ferraioli, G, Sakamaki, K, Itoi, T, Kage, M & Yano, H 2024, 'US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study', Radiology, vol. 312, no. 2, e233377. https://doi.org/10.1148/radiol.233377

TY - JOUR

T1 - US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease

T2 - The iLEAD Study

AU - Sugimoto, Katsutoshi

AU - Moriyasu, Fuminori

AU - Burgio, Marco Dioguardi

AU - Vilgrain, Valérie

AU - Jesper, Daniel

AU - Strobel, Deike

AU - Blank, Valentin

AU - Karlas, Thomas

AU - Grant, Edward G.

AU - Kelahan, Linda C.

AU - Gabriel, Helena

AU - Choi, Byung Ihn

AU - Nishimura, Takashi

AU - Iijima, Hiroko

AU - Dubinsky, Theodore J.

AU - Gao, Jing

AU - Lee, Dong Ho

AU - Lee, Jae Young

AU - Zhao, Yanan

AU - Huang, Pintong

AU - Zeng, Jie

AU - Lim, Adrian

AU - Xie, Xiaoyan

AU - Barr, Richard G.

AU - Cantisani, Vito

AU - Ferraioli, Giovanna

AU - Sakamaki, Kentaro

AU - Itoi, Takao

AU - Kage, Masayoshi

AU - Yano, Hirohisa

PY - 2024/8

Y1 - 2024/8

N2 - Background: Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose: To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods: This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results: A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion: Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation.

AB - Background: Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose: To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods: This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results: A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion: Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation.

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U2 - 10.1148/radiol.233377

DO - 10.1148/radiol.233377

M3 - Article

C2 - 39162633

AN - SCOPUS:85203018091

SN - 0033-8419

VL - 312

JO - Radiology

JF - Radiology

IS - 2

M1 - e233377

ER -

US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study

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