Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis

Ferenc E Mózes; Jenny A Lee; Yasaman Vali; Emmanuel A Selvaraj; Arjun N A Jayaswal; Jérôme Boursier; Victor de Lédinghen; Monica Lupșor-Platon; Yusuf Yilmaz; Wah-Kheong Chan; Sanjiv Mahadeva; Thomas Karlas; Johannes Wiegand; null Shalimar; Emmanouil Tsochatzis; Antonio Liguori; Vincent Wai-Sun Wong; Dae Ho Lee; Adriaan G Holleboom; Anne-Marieke van Dijk; Anne Linde Mak; Hannes Hagström; Camilla Akbari; Masashi Hirooka; Dong Hyeon Lee; Won Kim; Takeshi Okanoue; Toshihide Shima; Atsushi Nakajima; Masato Yoneda; Paul J Thuluvath; Feng Li; Annalisa Berzigotti; Yuly P Mendoza; Mazen Noureddin; Emily Truong; Céline Fournier-Poizat; Andreas Geier; Theresa Tuthill; Carla Yunis; Quentin M Anstee; Stephen A Harrison; Patrick M Bossuyt; Michael Pavlides

doi:10.1111/liv.15914

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis

Ferenc E Mózes, Jenny A Lee, Yasaman Vali, Emmanuel A Selvaraj, Arjun N A Jayaswal, Jérôme Boursier, Victor de Lédinghen, Monica Lupșor-Platon, Yusuf Yilmaz, Wah-Kheong Chan, Sanjiv Mahadeva, Thomas Karlas, Johannes Wiegand, Shalimar, Emmanouil Tsochatzis, Antonio Liguori, Vincent Wai-Sun Wong, Dae Ho Lee, Adriaan G Holleboom, Anne-Marieke van DijkAnne Linde Mak, Hannes Hagström, Camilla Akbari, Masashi Hirooka, Dong Hyeon Lee, Won Kim, Takeshi Okanoue, Toshihide Shima, Atsushi Nakajima, Masato Yoneda, Paul J Thuluvath, Feng Li, Annalisa Berzigotti, Yuly P Mendoza, Mazen Noureddin, Emily Truong, Céline Fournier-Poizat, Andreas Geier, Theresa Tuthill, Carla Yunis, Quentin M Anstee, Stephen A Harrison, Patrick M Bossuyt, Michael Pavlides

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

Abstract

BACKGROUND & AIMS: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions.

METHODS: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported.

RESULTS: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%.

CONCLUSIONS: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.

Original language	English
Journal	Liver international
Early online date	4 Apr 2024
DOIs	https://doi.org/10.1111/liv.15914
Publication status	E-pub ahead of print - 4 Apr 2024

Keywords

FAST
FIB-4
LSM-VCTE
MASH
NFS
at-risk MASH
non-invasive tests

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10.1111/liv.15914

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Mózes, F. E., Lee, J. A., Vali, Y., Selvaraj, E. A., Jayaswal, A. N. A., Boursier, J., de Lédinghen, V., Lupșor-Platon, M., Yilmaz, Y., Chan, W.-K., Mahadeva, S., Karlas, T., Wiegand, J., Shalimar, Tsochatzis, E., Liguori, A., Wong, V. W.-S., Lee, D. H., Holleboom, A. G., ... Pavlides, M. (2024). Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis. Liver international. Advance online publication. https://doi.org/10.1111/liv.15914

@article{72711c83c0f34858892e68fdf8959616,

title = "Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis",

abstract = "BACKGROUND & AIMS: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions.METHODS: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported.RESULTS: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%.CONCLUSIONS: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.",

keywords = "FAST, FIB-4, LSM-VCTE, MASH, NFS, at-risk MASH, non-invasive tests",

author = "M{\'o}zes, {Ferenc E} and Lee, {Jenny A} and Yasaman Vali and Selvaraj, {Emmanuel A} and Jayaswal, {Arjun N A} and J{\'e}r{\^o}me Boursier and {de L{\'e}dinghen}, Victor and Monica Lupșor-Platon and Yusuf Yilmaz and Wah-Kheong Chan and Sanjiv Mahadeva and Thomas Karlas and Johannes Wiegand and Shalimar and Emmanouil Tsochatzis and Antonio Liguori and Wong, {Vincent Wai-Sun} and Lee, {Dae Ho} and Holleboom, {Adriaan G} and {van Dijk}, Anne-Marieke and Mak, {Anne Linde} and Hannes Hagstr{\"o}m and Camilla Akbari and Masashi Hirooka and Lee, {Dong Hyeon} and Won Kim and Takeshi Okanoue and Toshihide Shima and Atsushi Nakajima and Masato Yoneda and Thuluvath, {Paul J} and Feng Li and Annalisa Berzigotti and Mendoza, {Yuly P} and Mazen Noureddin and Emily Truong and C{\'e}line Fournier-Poizat and Andreas Geier and Theresa Tuthill and Carla Yunis and Anstee, {Quentin M} and Harrison, {Stephen A} and Bossuyt, {Patrick M} and Michael Pavlides",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Liver International published by John Wiley & Sons Ltd.",

year = "2024",

month = apr,

day = "4",

doi = "10.1111/liv.15914",

language = "English",

journal = "Liver international",

issn = "1478-3223",

publisher = "Wiley-Blackwell",

}

Mózes, FE, Lee, JA , Vali, Y, Selvaraj, EA, Jayaswal, ANA, Boursier, J, de Lédinghen, V, Lupșor-Platon, M, Yilmaz, Y, Chan, W-K, Mahadeva, S, Karlas, T, Wiegand, J, Shalimar, Tsochatzis, E, Liguori, A, Wong, VW-S, Lee, DH, Holleboom, AG , van Dijk, A-M , Mak, AL, Hagström, H, Akbari, C, Hirooka, M, Lee, DH, Kim, W, Okanoue, T, Shima, T, Nakajima, A, Yoneda, M, Thuluvath, PJ, Li, F, Berzigotti, A, Mendoza, YP, Noureddin, M, Truong, E, Fournier-Poizat, C, Geier, A, Tuthill, T, Yunis, C, Anstee, QM, Harrison, SA, Bossuyt, PM & Pavlides, M 2024, 'Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis', Liver international. https://doi.org/10.1111/liv.15914

TY - JOUR

T1 - Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis

AU - Mózes, Ferenc E

AU - Lee, Jenny A

AU - Vali, Yasaman

AU - Selvaraj, Emmanuel A

AU - Jayaswal, Arjun N A

AU - Boursier, Jérôme

AU - de Lédinghen, Victor

AU - Lupșor-Platon, Monica

AU - Yilmaz, Yusuf

AU - Chan, Wah-Kheong

AU - Mahadeva, Sanjiv

AU - Karlas, Thomas

AU - Wiegand, Johannes

AU - Shalimar, null

AU - Tsochatzis, Emmanouil

AU - Liguori, Antonio

AU - Wong, Vincent Wai-Sun

AU - Lee, Dae Ho

AU - Holleboom, Adriaan G

AU - van Dijk, Anne-Marieke

AU - Mak, Anne Linde

AU - Hagström, Hannes

AU - Akbari, Camilla

AU - Hirooka, Masashi

AU - Lee, Dong Hyeon

AU - Kim, Won

AU - Okanoue, Takeshi

AU - Shima, Toshihide

AU - Nakajima, Atsushi

AU - Yoneda, Masato

AU - Thuluvath, Paul J

AU - Li, Feng

AU - Berzigotti, Annalisa

AU - Mendoza, Yuly P

AU - Noureddin, Mazen

AU - Truong, Emily

AU - Fournier-Poizat, Céline

AU - Geier, Andreas

AU - Tuthill, Theresa

AU - Yunis, Carla

AU - Anstee, Quentin M

AU - Harrison, Stephen A

AU - Bossuyt, Patrick M

AU - Pavlides, Michael

PY - 2024/4/4

Y1 - 2024/4/4

N2 - BACKGROUND & AIMS: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions.METHODS: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported.RESULTS: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%.CONCLUSIONS: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.

AB - BACKGROUND & AIMS: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions.METHODS: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported.RESULTS: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%.CONCLUSIONS: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.

KW - FAST

KW - FIB-4

KW - LSM-VCTE

KW - MASH

KW - NFS

KW - at-risk MASH

KW - non-invasive tests

UR - http://www.scopus.com/inward/record.url?scp=85189953074&partnerID=8YFLogxK

U2 - 10.1111/liv.15914

DO - 10.1111/liv.15914

M3 - Article

C2 - 38573034

SN - 1478-3223

JO - Liver international

JF - Liver international

ER -

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis

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Keywords

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