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

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 Inde...

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Main Authors: Mozes, Ferenc Emil, Lee, Jenny A., Selvaraj, Emmanuel Anandraj, Jayaswal, Arjun Narayan Ajmer, Trauner, Michael, Boursier, Jerome, Fournier, Celine, Staufer, Katharina, Stauber, Rudolf E., Bugianesi, Elisabetta, Younes, Ramy, Gaia, Silvia, Lupsor-Platon, Monica, Petta, Salvatore, Shima, Toshihide, Okanoue, Takeshi, Mahadeva, Sanjiv, Chan, Wah Kheong, Eddowes, Peter J., Hirschfield, Gideon M., Newsome, Philip Noel, Wong, Vincent Wai-Sun, de Ledinghen, Victor, Fan, Jiangao, Shen, Feng, Cobbold, Jeremy F., Sumida, Yoshio, Okajima, Akira, Schattenberg, Joern M., Labenz, Christian, Kim, Won, Lee, Myoung Seok, Wiegand, Johannes, Karlas, Thomas, Yilmaz, Yusuf, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Cassinotto, Christophe, Aggarwal, Sandeep, Garg, Harshit, Ooi, Geraldine J., Nakajima, Atsushi, Yoneda, Masato, Ziol, Marianne, Barget, Nathalie, Geier, Andreas, Tuthill, Theresa, Brosnan, M. Julia, Anstee, Quentin Mark, Neubauer, Stefan, Harrison, Stephen A., Bossuyt, Patrick M., Pavlides, Michael, Investigators, LITMUS
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Published: BMJ Publishing Group 2022
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Online Access:http://eprints.um.edu.my/42456/
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id my.um.eprints.42456
record_format eprints
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Mozes, Ferenc Emil
Lee, Jenny A.
Selvaraj, Emmanuel Anandraj
Jayaswal, Arjun Narayan Ajmer
Trauner, Michael
Boursier, Jerome
Fournier, Celine
Staufer, Katharina
Stauber, Rudolf E.
Bugianesi, Elisabetta
Younes, Ramy
Gaia, Silvia
Lupsor-Platon, Monica
Petta, Salvatore
Shima, Toshihide
Okanoue, Takeshi
Mahadeva, Sanjiv
Chan, Wah Kheong
Eddowes, Peter J.
Hirschfield, Gideon M.
Newsome, Philip Noel
Wong, Vincent Wai-Sun
de Ledinghen, Victor
Fan, Jiangao
Shen, Feng
Cobbold, Jeremy F.
Sumida, Yoshio
Okajima, Akira
Schattenberg, Joern M.
Labenz, Christian
Kim, Won
Lee, Myoung Seok
Wiegand, Johannes
Karlas, Thomas
Yilmaz, Yusuf
Aithal, Guruprasad Padur
Palaniyappan, Naaventhan
Cassinotto, Christophe
Aggarwal, Sandeep
Garg, Harshit
Ooi, Geraldine J.
Nakajima, Atsushi
Yoneda, Masato
Ziol, Marianne
Barget, Nathalie
Geier, Andreas
Tuthill, Theresa
Brosnan, M. Julia
Anstee, Quentin Mark
Neubauer, Stefan
Harrison, Stephen A.
Bossuyt, Patrick M.
Pavlides, Michael
Investigators, LITMUS
Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis
description 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/m(2); 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 (<1.3; >= 2.67) followed by LSM-VCTE cut-offs (<8.0; >= 10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; >= 3.48) followed by LSM cut-offs (<8.0; >= 20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. 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.
format Article
author Mozes, Ferenc Emil
Lee, Jenny A.
Selvaraj, Emmanuel Anandraj
Jayaswal, Arjun Narayan Ajmer
Trauner, Michael
Boursier, Jerome
Fournier, Celine
Staufer, Katharina
Stauber, Rudolf E.
Bugianesi, Elisabetta
Younes, Ramy
Gaia, Silvia
Lupsor-Platon, Monica
Petta, Salvatore
Shima, Toshihide
Okanoue, Takeshi
Mahadeva, Sanjiv
Chan, Wah Kheong
Eddowes, Peter J.
Hirschfield, Gideon M.
Newsome, Philip Noel
Wong, Vincent Wai-Sun
de Ledinghen, Victor
Fan, Jiangao
Shen, Feng
Cobbold, Jeremy F.
Sumida, Yoshio
Okajima, Akira
Schattenberg, Joern M.
Labenz, Christian
Kim, Won
Lee, Myoung Seok
Wiegand, Johannes
Karlas, Thomas
Yilmaz, Yusuf
Aithal, Guruprasad Padur
Palaniyappan, Naaventhan
Cassinotto, Christophe
Aggarwal, Sandeep
Garg, Harshit
Ooi, Geraldine J.
Nakajima, Atsushi
Yoneda, Masato
Ziol, Marianne
Barget, Nathalie
Geier, Andreas
Tuthill, Theresa
Brosnan, M. Julia
Anstee, Quentin Mark
Neubauer, Stefan
Harrison, Stephen A.
Bossuyt, Patrick M.
Pavlides, Michael
Investigators, LITMUS
author_facet Mozes, Ferenc Emil
Lee, Jenny A.
Selvaraj, Emmanuel Anandraj
Jayaswal, Arjun Narayan Ajmer
Trauner, Michael
Boursier, Jerome
Fournier, Celine
Staufer, Katharina
Stauber, Rudolf E.
Bugianesi, Elisabetta
Younes, Ramy
Gaia, Silvia
Lupsor-Platon, Monica
Petta, Salvatore
Shima, Toshihide
Okanoue, Takeshi
Mahadeva, Sanjiv
Chan, Wah Kheong
Eddowes, Peter J.
Hirschfield, Gideon M.
Newsome, Philip Noel
Wong, Vincent Wai-Sun
de Ledinghen, Victor
Fan, Jiangao
Shen, Feng
Cobbold, Jeremy F.
Sumida, Yoshio
Okajima, Akira
Schattenberg, Joern M.
Labenz, Christian
Kim, Won
Lee, Myoung Seok
Wiegand, Johannes
Karlas, Thomas
Yilmaz, Yusuf
Aithal, Guruprasad Padur
Palaniyappan, Naaventhan
Cassinotto, Christophe
Aggarwal, Sandeep
Garg, Harshit
Ooi, Geraldine J.
Nakajima, Atsushi
Yoneda, Masato
Ziol, Marianne
Barget, Nathalie
Geier, Andreas
Tuthill, Theresa
Brosnan, M. Julia
Anstee, Quentin Mark
Neubauer, Stefan
Harrison, Stephen A.
Bossuyt, Patrick M.
Pavlides, Michael
Investigators, LITMUS
author_sort Mozes, Ferenc Emil
title Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis
title_short Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis
title_full Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis
title_fullStr Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis
title_full_unstemmed Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis
title_sort diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with nafld: an individual patient data meta-analysis
publisher BMJ Publishing Group
publishDate 2022
url http://eprints.um.edu.my/42456/
_version_ 1781704646128041984
spelling my.um.eprints.424562023-10-09T07:07:01Z http://eprints.um.edu.my/42456/ Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis Mozes, Ferenc Emil Lee, Jenny A. Selvaraj, Emmanuel Anandraj Jayaswal, Arjun Narayan Ajmer Trauner, Michael Boursier, Jerome Fournier, Celine Staufer, Katharina Stauber, Rudolf E. Bugianesi, Elisabetta Younes, Ramy Gaia, Silvia Lupsor-Platon, Monica Petta, Salvatore Shima, Toshihide Okanoue, Takeshi Mahadeva, Sanjiv Chan, Wah Kheong Eddowes, Peter J. Hirschfield, Gideon M. Newsome, Philip Noel Wong, Vincent Wai-Sun de Ledinghen, Victor Fan, Jiangao Shen, Feng Cobbold, Jeremy F. Sumida, Yoshio Okajima, Akira Schattenberg, Joern M. Labenz, Christian Kim, Won Lee, Myoung Seok Wiegand, Johannes Karlas, Thomas Yilmaz, Yusuf Aithal, Guruprasad Padur Palaniyappan, Naaventhan Cassinotto, Christophe Aggarwal, Sandeep Garg, Harshit Ooi, Geraldine J. Nakajima, Atsushi Yoneda, Masato Ziol, Marianne Barget, Nathalie Geier, Andreas Tuthill, Theresa Brosnan, M. Julia Anstee, Quentin Mark Neubauer, Stefan Harrison, Stephen A. Bossuyt, Patrick M. Pavlides, Michael Investigators, LITMUS R Medicine 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/m(2); 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 (<1.3; >= 2.67) followed by LSM-VCTE cut-offs (<8.0; >= 10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; >= 3.48) followed by LSM cut-offs (<8.0; >= 20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. 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. BMJ Publishing Group 2022-05 Article PeerReviewed Mozes, Ferenc Emil and Lee, Jenny A. and Selvaraj, Emmanuel Anandraj and Jayaswal, Arjun Narayan Ajmer and Trauner, Michael and Boursier, Jerome and Fournier, Celine and Staufer, Katharina and Stauber, Rudolf E. and Bugianesi, Elisabetta and Younes, Ramy and Gaia, Silvia and Lupsor-Platon, Monica and Petta, Salvatore and Shima, Toshihide and Okanoue, Takeshi and Mahadeva, Sanjiv and Chan, Wah Kheong and Eddowes, Peter J. and Hirschfield, Gideon M. and Newsome, Philip Noel and Wong, Vincent Wai-Sun and de Ledinghen, Victor and Fan, Jiangao and Shen, Feng and Cobbold, Jeremy F. and Sumida, Yoshio and Okajima, Akira and Schattenberg, Joern M. and Labenz, Christian and Kim, Won and Lee, Myoung Seok and Wiegand, Johannes and Karlas, Thomas and Yilmaz, Yusuf and Aithal, Guruprasad Padur and Palaniyappan, Naaventhan and Cassinotto, Christophe and Aggarwal, Sandeep and Garg, Harshit and Ooi, Geraldine J. and Nakajima, Atsushi and Yoneda, Masato and Ziol, Marianne and Barget, Nathalie and Geier, Andreas and Tuthill, Theresa and Brosnan, M. Julia and Anstee, Quentin Mark and Neubauer, Stefan and Harrison, Stephen A. and Bossuyt, Patrick M. and Pavlides, Michael and Investigators, LITMUS (2022) Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. GUT, 71 (5). pp. 1006-1019. ISSN 0017-5749, DOI https://doi.org/10.1136/gutjnl-2021-324243 <https://doi.org/10.1136/gutjnl-2021-324243>. 10.1136/gutjnl-2021-324243
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