Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes

Grazia Pennisi; Marco Enea; Vincenzo Falco; Guruprasad P Aithal; Naaventhan Palaniyappan; Yusuf Yilmaz; Jerome Boursier; Christophe Cassinotto; Victor de Lédinghen; Wah Kheong Chan; Sanjiv Mahadeva; Peter Eddowes; Philip Newsome; Thomas Karlas; Johannes Wiegand; Vincent Wai-Sun Wong; Jörn M Schattenberg; Christian Labenz; Won Kim; Myoung Seok Lee; Monica Lupsor-Platon; Jeremy F L Cobbold; Jian-Gao Fan; Feng Shen; Katharina Staufer; Michael Trauner; Rudolf Stauber; Atsushi Nakajima; Masato Yoneda; Elisabetta Bugianesi; Ramy Younes; Silvia Gaia; Ming-Hua Zheng; Calogero Cammà; Quentin M Anstee; Ferenc Emil Mózes; Michael Pavlides; Salvatore Petta

doi:10.1097/HEP.0000000000000351

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes

Grazia Pennisi, Marco Enea, Vincenzo Falco, Guruprasad P Aithal, Naaventhan Palaniyappan, Yusuf Yilmaz, Jerome Boursier, Christophe Cassinotto, Victor de Lédinghen, Wah Kheong Chan, Sanjiv Mahadeva, Peter Eddowes, Philip Newsome, Thomas Karlas, Johannes Wiegand, Vincent Wai-Sun Wong, Jörn M Schattenberg, Christian Labenz, Won Kim, Myoung Seok LeeMonica Lupsor-Platon, Jeremy F L Cobbold, Jian-Gao Fan, Feng Shen, Katharina Staufer, Michael Trauner, Rudolf Stauber, Atsushi Nakajima, Masato Yoneda, Elisabetta Bugianesi, Ramy Younes, Silvia Gaia, Ming-Hua Zheng, Calogero Cammà, Quentin M Anstee, Ferenc Emil Mózes, Michael Pavlides, Salvatore Petta^*

^*Corresponding author for this work

Medical and Dental Sciences

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

Abstract

BACKGROUND: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D).

METHODS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of NITs individually or in sequential combination was assessed by area under receiver operating characteristic curve(AUROC) and by decision curve analysis(DCA). Comparison with 2278 NAFLD patients without T2D was also made.

RESULTS: In NAFLD with T2D LSM and AGILE 3+ outperformed both NFS and FIB-4 for advanced fibrosis(AUROC:LSM 0.82,AGILE 3+ 0.82,NFS 0.72,FIB-4 0.75,APRI 0.68;p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%.The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40% to 60% in necessary LSM tests. DCA showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH(AUROC LSM 0.79,AGILE 3+ 0.77,NFS 0.71,FIB-4 0.71;p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were sub-optimal for diagnosing NASH.

CONCLUSIONS: LSM and AGILE 3+ individually or in low availability setting in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

Original language	English
Pages (from-to)	195-211
Number of pages	17
Journal	Hepatology
Volume	78
Issue number	1
Early online date	17 Mar 2023
DOIs	https://doi.org/10.1097/HEP.0000000000000351
Publication status	Published - Jul 2023

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10.1097/HEP.0000000000000351

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Pennisi, G., Enea, M., Falco, V., Aithal, G. P., Palaniyappan, N., Yilmaz, Y., Boursier, J., Cassinotto, C., de Lédinghen, V., Chan, W. K., Mahadeva, S., Eddowes, P., Newsome, P., Karlas, T., Wiegand, J., Wong, V. W.-S., Schattenberg, J. M., Labenz, C., Kim, W., ... Petta, S. (2023). Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Hepatology, 78(1), 195-211. https://doi.org/10.1097/HEP.0000000000000351

@article{ceb3d80b924a4b579bfc8086339e259e,

title = "Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes",

abstract = "BACKGROUND: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D).METHODS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of NITs individually or in sequential combination was assessed by area under receiver operating characteristic curve(AUROC) and by decision curve analysis(DCA). Comparison with 2278 NAFLD patients without T2D was also made.RESULTS: In NAFLD with T2D LSM and AGILE 3+ outperformed both NFS and FIB-4 for advanced fibrosis(AUROC:LSM 0.82,AGILE 3+ 0.82,NFS 0.72,FIB-4 0.75,APRI 0.68;p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%.The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40% to 60% in necessary LSM tests. DCA showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH(AUROC LSM 0.79,AGILE 3+ 0.77,NFS 0.71,FIB-4 0.71;p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were sub-optimal for diagnosing NASH.CONCLUSIONS: LSM and AGILE 3+ individually or in low availability setting in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.",

author = "Grazia Pennisi and Marco Enea and Vincenzo Falco and Aithal, {Guruprasad P} and Naaventhan Palaniyappan and Yusuf Yilmaz and Jerome Boursier and Christophe Cassinotto and {de L{\'e}dinghen}, Victor and Chan, {Wah Kheong} and Sanjiv Mahadeva and Peter Eddowes and Philip Newsome and Thomas Karlas and Johannes Wiegand and Wong, {Vincent Wai-Sun} and Schattenberg, {J{\"o}rn M} and Christian Labenz and Won Kim and Lee, {Myoung Seok} and Monica Lupsor-Platon and Cobbold, {Jeremy F L} and Jian-Gao Fan and Feng Shen and Katharina Staufer and Michael Trauner and Rudolf Stauber and Atsushi Nakajima and Masato Yoneda and Elisabetta Bugianesi and Ramy Younes and Silvia Gaia and Ming-Hua Zheng and Calogero Camm{\`a} and Anstee, {Quentin M} and M{\'o}zes, {Ferenc Emil} and Michael Pavlides and Salvatore Petta",

note = "Copyright {\textcopyright} 2023 American Association for the Study of Liver Diseases.",

year = "2023",

month = jul,

doi = "10.1097/HEP.0000000000000351",

language = "English",

volume = "78",

pages = "195--211",

journal = "Hepatology",

issn = "0270-9139",

publisher = "Wiley",

number = "1",

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Pennisi, G, Enea, M, Falco, V, Aithal, GP, Palaniyappan, N, Yilmaz, Y, Boursier, J, Cassinotto, C, de Lédinghen, V, Chan, WK, Mahadeva, S, Eddowes, P, Newsome, P, Karlas, T, Wiegand, J, Wong, VW-S, Schattenberg, JM, Labenz, C, Kim, W, Lee, MS, Lupsor-Platon, M, Cobbold, JFL, Fan, J-G, Shen, F, Staufer, K, Trauner, M, Stauber, R, Nakajima, A, Yoneda, M, Bugianesi, E, Younes, R, Gaia, S, Zheng, M-H, Cammà, C, Anstee, QM, Mózes, FE, Pavlides, M & Petta, S 2023, 'Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes', Hepatology, vol. 78, no. 1, pp. 195-211. https://doi.org/10.1097/HEP.0000000000000351

TY - JOUR

T1 - Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes

AU - Pennisi, Grazia

AU - Enea, Marco

AU - Falco, Vincenzo

AU - Aithal, Guruprasad P

AU - Palaniyappan, Naaventhan

AU - Yilmaz, Yusuf

AU - Boursier, Jerome

AU - Cassinotto, Christophe

AU - de Lédinghen, Victor

AU - Chan, Wah Kheong

AU - Mahadeva, Sanjiv

AU - Eddowes, Peter

AU - Newsome, Philip

AU - Karlas, Thomas

AU - Wiegand, Johannes

AU - Wong, Vincent Wai-Sun

AU - Schattenberg, Jörn M

AU - Labenz, Christian

AU - Kim, Won

AU - Lee, Myoung Seok

AU - Lupsor-Platon, Monica

AU - Cobbold, Jeremy F L

AU - Fan, Jian-Gao

AU - Shen, Feng

AU - Staufer, Katharina

AU - Trauner, Michael

AU - Stauber, Rudolf

AU - Nakajima, Atsushi

AU - Yoneda, Masato

AU - Bugianesi, Elisabetta

AU - Younes, Ramy

AU - Gaia, Silvia

AU - Zheng, Ming-Hua

AU - Cammà, Calogero

AU - Anstee, Quentin M

AU - Mózes, Ferenc Emil

AU - Pavlides, Michael

AU - Petta, Salvatore

PY - 2023/7

Y1 - 2023/7

N2 - BACKGROUND: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D).METHODS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of NITs individually or in sequential combination was assessed by area under receiver operating characteristic curve(AUROC) and by decision curve analysis(DCA). Comparison with 2278 NAFLD patients without T2D was also made.RESULTS: In NAFLD with T2D LSM and AGILE 3+ outperformed both NFS and FIB-4 for advanced fibrosis(AUROC:LSM 0.82,AGILE 3+ 0.82,NFS 0.72,FIB-4 0.75,APRI 0.68;p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%.The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40% to 60% in necessary LSM tests. DCA showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH(AUROC LSM 0.79,AGILE 3+ 0.77,NFS 0.71,FIB-4 0.71;p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were sub-optimal for diagnosing NASH.CONCLUSIONS: LSM and AGILE 3+ individually or in low availability setting in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

AB - BACKGROUND: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D).METHODS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of NITs individually or in sequential combination was assessed by area under receiver operating characteristic curve(AUROC) and by decision curve analysis(DCA). Comparison with 2278 NAFLD patients without T2D was also made.RESULTS: In NAFLD with T2D LSM and AGILE 3+ outperformed both NFS and FIB-4 for advanced fibrosis(AUROC:LSM 0.82,AGILE 3+ 0.82,NFS 0.72,FIB-4 0.75,APRI 0.68;p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%.The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40% to 60% in necessary LSM tests. DCA showed that all scores had modest net benefit for ruling-out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH(AUROC LSM 0.79,AGILE 3+ 0.77,NFS 0.71,FIB-4 0.71;p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were sub-optimal for diagnosing NASH.CONCLUSIONS: LSM and AGILE 3+ individually or in low availability setting in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

U2 - 10.1097/HEP.0000000000000351

DO - 10.1097/HEP.0000000000000351

M3 - Article

C2 - 36924031

SN - 0270-9139

VL - 78

SP - 195

EP - 211

JO - Hepatology

JF - Hepatology

IS - 1

ER -

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes

Abstract

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