Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis
Ferenc E. Mózes, Jenny Lee, Emmanuel Selvaraj, Arjun Jayaswal, Michael Trauner, Jérôme Boursier, Céline Fournier, Katharina Staufer, Rudolf Stauber, Elisabetta Bugianesi, Ramy Younes, Silvia Gaia, Monica Lupșor‐Platon, Salvatore Petta, Toshihide Shima, Takeshi Okanoue, Sanjiv Mahadeva, Wah‐Kheong Chan, Peter Eddowes, Gideon M. Hirschfield, Philip N. Newsome, Vincent Wai‐Sun Wong, Victor de Lédinghen, Jian‐Gao Fan, Feng Shen, Jeremy Cobbold, Yoshio Sumida, Akira Okajima, Jörn M. Schattenberg, Christian Labenz, Won Kim, Myoung Seok Lee, Johannes Wiegand, Thomas Karlas, Yusuf Yılmaz, Guruprasad P. Aithal, Naaventhan Palaniyappan, Christophe Cassinotto, Sandeep Aggarwal, Harshit Garg, Geraldine Ooi, Atsushi Nakajima, Masato Yoneda, Marianne Ziol, Nathalie Barget, Andreas Geier, Theresa Tuthill, M. Julia Brosnan, Quentin M. Anstee, Stefan Neubauer, Stephen A. Harrison, Patrick M. Bossuyt, Michael Pavlides
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: ; 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.