Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

LITMUS Investigators; Stephen A. Harrison; Patrick M. Bossuyt; Michael Pavlides

doi:10.1136/gutjnl-2021-324243

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

LITMUS Investigators, Stephen A. Harrison, Patrick M. Bossuyt, Michael Pavlides^*

^*Corresponding author for this work

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Abstract

Objective: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.

Design: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.

Results: Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (
Conclusion: Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

Original language	English
Pages (from-to)	1006-1019
Number of pages	14
Journal	Gut
Volume	71
Issue number	5
DOIs	https://doi.org/10.1136/gutjnl-2021-324243
Publication status	Published - 17 May 2021

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@article{29d1aa1db97141bfaafe0f92397767f5,

title = "Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis",

abstract = "Objective: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.Design: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.Results: Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (Conclusion: Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.",

author = "{LITMUS Investigators} and M{\'o}zes, {Ferenc Emil} and Lee, {Jenny A} and Selvaraj, {Emmanuel Anandraj} and Jayaswal, {Arjun Narayan Ajmer} and Michael Trauner and Jerome Boursier and C{\'e}line Fournier and Katharina Staufer and Stauber, {Rudolf E} and Elisabetta Bugianesi and Ramy Younes and Silvia Gaia and Monica Lupșor-Platon and Salvatore Petta and Toshihide Shima and Takeshi Okanoue and Sanjiv Mahadeva and Wah-kheong Chan and Eddowes, {Peter J} and Hirschfield, {Gideon M} and Newsome, {Philip Noel} and Wong, {Vincent Wai-sun} and {De ledinghen}, Victor and Jiangao Fan and Feng Shen and Cobbold, {Jeremy F} and Yoshio Sumida and Akira Okajima and Schattenberg, {J{\"o}rn M} and Christian Labenz and Won Kim and Lee, {Myoung Seok} and Johannes Wiegand and Thomas Karlas and Yusuf Yılmaz and Aithal, {Guruprasad Padur} and Naaventhan Palaniyappan and Christophe Cassinotto and Sandeep Aggarwal and Harshit Garg and Ooi, {Geraldine J} and Atsushi Nakajima and Masato Yoneda and Marianne Ziol and Nathalie Barget and Andreas Geier and Theresa Tuthill and Brosnan, {M. Julia} and Anstee, {Quentin Mark} and Stefan Neubauer and Harrison, {Stephen A.} and Bossuyt, {Patrick M.} and Michael Pavlides",

year = "2021",

month = may,

day = "17",

doi = "10.1136/gutjnl-2021-324243",

language = "English",

volume = "71",

pages = "1006--1019",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "5",

}

TY - JOUR

T1 - Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD

T2 - an individual patient data meta-analysis

AU - LITMUS Investigators

AU - Mózes, Ferenc Emil

AU - Lee, Jenny A

AU - Selvaraj, Emmanuel Anandraj

AU - Jayaswal, Arjun Narayan Ajmer

AU - Trauner, Michael

AU - Boursier, Jerome

AU - Fournier, Céline

AU - Staufer, Katharina

AU - Stauber, Rudolf E

AU - Bugianesi, Elisabetta

AU - Younes, Ramy

AU - Gaia, Silvia

AU - Lupșor-Platon, Monica

AU - Petta, Salvatore

AU - Shima, Toshihide

AU - Okanoue, Takeshi

AU - Mahadeva, Sanjiv

AU - Chan, Wah-kheong

AU - Eddowes, Peter J

AU - Hirschfield, Gideon M

AU - Newsome, Philip Noel

AU - Wong, Vincent Wai-sun

AU - De ledinghen, Victor

AU - Fan, Jiangao

AU - Shen, Feng

AU - Cobbold, Jeremy F

AU - Sumida, Yoshio

AU - Okajima, Akira

AU - Schattenberg, Jörn M

AU - Labenz, Christian

AU - Kim, Won

AU - Lee, Myoung Seok

AU - Wiegand, Johannes

AU - Karlas, Thomas

AU - Yılmaz, Yusuf

AU - Aithal, Guruprasad Padur

AU - Palaniyappan, Naaventhan

AU - Cassinotto, Christophe

AU - Aggarwal, Sandeep

AU - Garg, Harshit

AU - Ooi, Geraldine J

AU - Nakajima, Atsushi

AU - Yoneda, Masato

AU - Ziol, Marianne

AU - Barget, Nathalie

AU - Geier, Andreas

AU - Tuthill, Theresa

AU - Brosnan, M. Julia

AU - Anstee, Quentin Mark

AU - Neubauer, Stefan

AU - Harrison, Stephen A.

AU - Bossuyt, Patrick M.

AU - Pavlides, Michael

PY - 2021/5/17

Y1 - 2021/5/17

N2 - Objective: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.Design: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.Results: Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (Conclusion: Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

AB - Objective: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.Design: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.Results: Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (Conclusion: Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

UR - http://europepmc.org/abstract/med/34001645

U2 - 10.1136/gutjnl-2021-324243

DO - 10.1136/gutjnl-2021-324243

M3 - Article

C2 - 34001645

SN - 0017-5749

VL - 71

SP - 1006

EP - 1019

JO - Gut

JF - Gut

IS - 5

ER -

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

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