Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference

M Munteanu, D Tiniakos, Q Anstee, F Charlotte, G Marchesini, E Bugianesi, M Trauner, M Romero Gomez, C Oliveira, C Day, J-F Dufour, S Bellentani, Y Ngo, S Traussnig, H Perazzo, O Deckmyn, P Bedossa, V Ratziu, T Poynard, FLIP Consortium and the FibroFrance Group, Vlad Ratziu, Thierry Poynard, Jean-Marie Castille, Yen Ngo, Tania Langon, Chris Day, Dina Tiniakos, Debbie Lawlor, Giulio Marchesini, Fabio Marra, Elisabetta Bugianesi, Stefano Bellentani, Jean-François Dufour, Manuel Romero Gomez, Thorkild Sørensen, Claudio Tribelli, Samuele De Minicis, Michael Trauner, Claudia Oliveira, Pierre Bedossa, Alastair D Burt, Annette S H Gouw, Carolin Lackner, Peter Schirmacher, Luigi Terracciano, Dina Tiniakos, J Brain, Yvonne Bury, Daniela Cabibi, Frederic Charlotte, Ezio David, Luisa Losi, Matteo Montani, Marıa Jesus Pareja, Dominique Wendum, Fritz Wrba, Marianne Ziol, Vlad Ratziu, Thierry Poynard, Vlad Ratziu, Dominique Thabut, Joseph Moussalli, Pascal Lebray, Marika Rudler, Françoise Imbert Bismuth, Frederic Charlotte, Olivier Rosmorduc, Yvon Calmus, Agnes Hartemann, Sophie Jacqueminet, Eric Bruckert, Philippe Giral, Sylvie Naveau, Gabriel Perlemuter, Brigitte Varsat, Anne Mercadier, M Munteanu, D Tiniakos, Q Anstee, F Charlotte, G Marchesini, E Bugianesi, M Trauner, M Romero Gomez, C Oliveira, C Day, J-F Dufour, S Bellentani, Y Ngo, S Traussnig, H Perazzo, O Deckmyn, P Bedossa, V Ratziu, T Poynard, FLIP Consortium and the FibroFrance Group, Vlad Ratziu, Thierry Poynard, Jean-Marie Castille, Yen Ngo, Tania Langon, Chris Day, Dina Tiniakos, Debbie Lawlor, Giulio Marchesini, Fabio Marra, Elisabetta Bugianesi, Stefano Bellentani, Jean-François Dufour, Manuel Romero Gomez, Thorkild Sørensen, Claudio Tribelli, Samuele De Minicis, Michael Trauner, Claudia Oliveira, Pierre Bedossa, Alastair D Burt, Annette S H Gouw, Carolin Lackner, Peter Schirmacher, Luigi Terracciano, Dina Tiniakos, J Brain, Yvonne Bury, Daniela Cabibi, Frederic Charlotte, Ezio David, Luisa Losi, Matteo Montani, Marıa Jesus Pareja, Dominique Wendum, Fritz Wrba, Marianne Ziol, Vlad Ratziu, Thierry Poynard, Vlad Ratziu, Dominique Thabut, Joseph Moussalli, Pascal Lebray, Marika Rudler, Françoise Imbert Bismuth, Frederic Charlotte, Olivier Rosmorduc, Yvon Calmus, Agnes Hartemann, Sophie Jacqueminet, Eric Bruckert, Philippe Giral, Sylvie Naveau, Gabriel Perlemuter, Brigitte Varsat, Anne Mercadier

Abstract

Background: Blood tests of liver injury are less well validated in non-alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis.

Aims: To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading.

Methods: We pre-included new NAFLD patients with biopsy and blood tests from a single-centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary-ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing.

Results: A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864-0.892) for FibroTest and fibrosis stages, 0.846 (0.830-0.862) for ActiTest and activity grades, and 0.822 (0.804-0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820-0.852; P = 0.0001), FIB4 (0.845; 0.829-0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850-0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05).

Conclusions: In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non-invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis.

© 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Flow charts of patient inclusions.
Figure 2
Figure 2
Box plots of FibroTest (a), ActiTest (b) and SteatoTest (c) according to the respective SAF scoring systems. 600 cases were included. Significance between stages/grades were estimated using NonBinROC measures and detailed in Table 2. The median FibroTest values increased steadily (NonBinROC P < 0.001) with fibrosis stages after F1, ranging from 0.18 in F0 (n = 122), 0.21 in F1 (n = 184), 0.28 in F2 (n = 140), 0.41 in F3 (n = 121) and 0.71 in cirrhosis (n = 33), all differences between adjacent stages were significant (Bonferroni test P < 0.05). The median value of ActiTest increased steadily (NonBinROC P < 0.001) from 0.21 for A0 (n = 64), 0.28 for A1 (n = 86), 0.35 for A2 (n = 191) and 0.38 for A3 (n = 156) and 0.46 for A4 (n = 103). Only the differences between 2 grades were significant (Bonferroni test P < 0.05). The median value of SteatoTest increased (NonBinROC P = 0.002) from 0.52 for S0 (n = 20), 0.62 for S1 (n = 188), 0.66 for S2 (n = 228), to 0.71 for S3 (n = 163). The only significant difference was observed between grades was between S3 and S1 (Bonferroni test P < 0.05).

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Source: PubMed

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