Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis

BACKGROUND & AIMS:<br>The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to estimate the accuracy of this test against biopsy. <br>&...

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Main Authors: Vali, V, Lee, J, Boursier, J, Spijker, R, Löffler, J, Verheij, J, Brosnan, MJ, Böcskei, Z, Anstee, QM, Bossuyt, PM, Zafarmand, MH, Pavlides, M, LITMUS systematic review team(†)
Format: Journal article
Language:English
Published: Elsevier 2020
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author Vali, V
Lee, J
Boursier, J
Spijker, R
Löffler, J
Verheij, J
Brosnan, MJ
Böcskei, Z
Anstee, QM
Bossuyt, PM
Zafarmand, MH
Pavlides, M
LITMUS systematic review team(†)
author_facet Vali, V
Lee, J
Boursier, J
Spijker, R
Löffler, J
Verheij, J
Brosnan, MJ
Böcskei, Z
Anstee, QM
Bossuyt, PM
Zafarmand, MH
Pavlides, M
LITMUS systematic review team(†)
author_sort Vali, V
collection OXFORD
description BACKGROUND & AIMS:<br>The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to estimate the accuracy of this test against biopsy. <br><br>METHODS:<br>In this systematic review, we searched MEDLINE, Embase, Web of Science and the Cochrane Library for studies that included patients with NAFLD and that used both liver biopsy (as the reference standard) and the ELF test. Two authors independently screened the references, extracted the data and assessed the quality of included studies. Due to the variation in reported thresholds, we used a multiple thresholds random effects model for meta-analysis (diagmeta R-package). <br><br>RESULTS:<br>The meta-analysis of 11 studies reporting advanced fibrosis and 5 studies reporting significant fibrosis showed that the ELF test had a sensitivity of &gt;0.90 for excluding fibrosis at a threshold of 7.7. However, as a diagnostic test at high thresholds, the test only achieved specificity and positive predictive value &gt;0.80 in very high prevalence settings (&gt;50%). To achieve a specificity of 0.90 for advanced and significant fibrosis, thresholds of 10.18 (sensitivity: 0.57) and 9.86 (sensitivity: 0.55) were required, respectively. <br><br>CONCLUSION:<br>The ELF test showed high sensitivity but limited specificity to exclude advanced and significant fibrosis at low cut-offs. The diagnostic performance of the test at higher thresholds was found to be more limited in low-prevalence settings. We conclude that clinicians should carefully consider the likely disease prevalence in their practice setting and adopt suitable test thresholds to achieve the desired performance. <br><br>LAY SUMMARY:<br>The enhanced liver fibrosis test has been suggested as a non-invasive blood test to aid the diagnosis of severe liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Our study results showed that the test has a high negative predictive value, especially in populations with low disease prevalence (likely encountered in primary care); so, it can exclude advanced fibrosis in patients with NAFLD. However, when prevalence is low, the positive predictive value of the enhanced liver fibrosis test is low, suggesting that additional strategies may be needed to make a positive diagnosis in such settings.
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spelling oxford-uuid:f81909d9-779f-42e8-83aa-e7dd80cf49492022-03-27T12:47:58ZEnhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f81909d9-779f-42e8-83aa-e7dd80cf4949EnglishSymplectic ElementsElsevier2020Vali, VLee, JBoursier, JSpijker, RLöffler, JVerheij, JBrosnan, MJBöcskei, ZAnstee, QMBossuyt, PMZafarmand, MHPavlides, MLITMUS systematic review team(†)BACKGROUND & AIMS:<br>The enhanced liver fibrosis (ELF) test has been proposed for the non-invasive assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to estimate the accuracy of this test against biopsy. <br><br>METHODS:<br>In this systematic review, we searched MEDLINE, Embase, Web of Science and the Cochrane Library for studies that included patients with NAFLD and that used both liver biopsy (as the reference standard) and the ELF test. Two authors independently screened the references, extracted the data and assessed the quality of included studies. Due to the variation in reported thresholds, we used a multiple thresholds random effects model for meta-analysis (diagmeta R-package). <br><br>RESULTS:<br>The meta-analysis of 11 studies reporting advanced fibrosis and 5 studies reporting significant fibrosis showed that the ELF test had a sensitivity of &gt;0.90 for excluding fibrosis at a threshold of 7.7. However, as a diagnostic test at high thresholds, the test only achieved specificity and positive predictive value &gt;0.80 in very high prevalence settings (&gt;50%). To achieve a specificity of 0.90 for advanced and significant fibrosis, thresholds of 10.18 (sensitivity: 0.57) and 9.86 (sensitivity: 0.55) were required, respectively. <br><br>CONCLUSION:<br>The ELF test showed high sensitivity but limited specificity to exclude advanced and significant fibrosis at low cut-offs. The diagnostic performance of the test at higher thresholds was found to be more limited in low-prevalence settings. We conclude that clinicians should carefully consider the likely disease prevalence in their practice setting and adopt suitable test thresholds to achieve the desired performance. <br><br>LAY SUMMARY:<br>The enhanced liver fibrosis test has been suggested as a non-invasive blood test to aid the diagnosis of severe liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Our study results showed that the test has a high negative predictive value, especially in populations with low disease prevalence (likely encountered in primary care); so, it can exclude advanced fibrosis in patients with NAFLD. However, when prevalence is low, the positive predictive value of the enhanced liver fibrosis test is low, suggesting that additional strategies may be needed to make a positive diagnosis in such settings.
spellingShingle Vali, V
Lee, J
Boursier, J
Spijker, R
Löffler, J
Verheij, J
Brosnan, MJ
Böcskei, Z
Anstee, QM
Bossuyt, PM
Zafarmand, MH
Pavlides, M
LITMUS systematic review team(†)
Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis
title Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis
title_full Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis
title_fullStr Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis
title_full_unstemmed Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis
title_short Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis
title_sort enhanced liver fibrosis test for the non invasive diagnosis of fibrosis in patients with nafld a systematic review and meta analysis
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