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

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

Gut, May 2021, Epub ahead of print. DOI: 10.1136/gutjnl-2021-324243



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.


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.


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 (<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.


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.