@article{3103118,
    title = "Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: An individual patient data meta-analysis",
    author = "Mózes, F.E. and Lee, J.A. and Selvaraj, E.A. and Jayaswal, A.N.A. and Trauner, M. and Boursier, J. and Fournier, C. and Staufer, K. and Stauber, R.E. and Bugianesi, E. and Younes, R. and Gaia, S. and Lupșor-Platon, M. and Petta, S. and Shima, T. and Okanoue, T. and Mahadeva, S. and Chan, W.-K. and Eddowes, P.J. and Newsome, P.N. and Wong, V.W.-S. and de Ledinghen, V. and Fan, J. and Shen, F. and Cobbold, J.F. and Sumida, Y. and Okajima, A. and Schattenberg, J.M. and Labenz, C. and Kim, W. and Lee, M.S. and Wiegand, J. and Karlas, T. and Yılmaz, Y. and Aithal, G.P. and Palaniyappan, N. and Cassinotto, C. and Aggarwal, S. and Garg, H. and Ooi, G.J. and Nakajima, A. and Yoneda, M. and Ziol, M. and Barget, N. and Geier, A. and Tuthill, T. and Brosnan, M.J. and Anstee, Q.M. and Neubauer, S. and Harrison, S.A. and Bossuyt, P.M. and Pavlides, M. and Anstee, Q. and Daly, A. and Johnson, K. and Govaere, O. and Cockell, S. and Tiniakos, D. and Bedossa, P. and Oakley, F. and Cordell, H. and Day, C. and Wonders, K. and Bossuyt, P. and Zafarmand, H. and Vali, Y. and Lee, J. and Ratziu, V. and Clement, K. and Pais, R. and Schuppan, D. and Schattenberg, J. and Schuppan, D. and Schattenberg, J. and Vidal-Puig, T. and Vacca, M. and Rodrigues-Cuenca, S. and Allison, M. and Kamzolas, I. and Petsalaki, E. and Oresic, M. and Hyötyläinen, T. and McGlinchey, A. and Mato, J.M. and Millet, O. and Dufour, J.-F. and Berzigotti, A. and Pavlides, M. and Harrison, S. and Neubauer, S. and Cobbold, J. and Mozes, F. and Akhtar, S. and Banerjee, R. and Kelly, M. and Shumbayawonda, E. and Dennis, A. and Erpicum, C. and Graham, M. and Romero-Gómez, M. and Gómez-González, E. and Ampuero, J. and Castell, J. and Gallego-Durán, R. and Fernández, I. and Montero-Vallejo, R. and Karsdal, M. and Erhardtsen, E. and Rasmussen, D. and Leeming, D.J. and Fisker, M.J. and Sinisi, A. and Musa, K. and Betsou, F. and Sandt, E. and Tonini, M. and Bugianesi, E. and Rosso, C. and Armandi, A. and Marra, F. and Gastaldelli, A. and Svegliati, G. and Boursier, J. and Francque, S. and Vonghia, L. and Ekstedt, M. and Kechagias, S. and Yki-Jarvinen, H. and Porthan, K. and van Mil, S. and Papatheodoridis, G. and Cortez-Pinto, H. and Valenti, L. and Petta, S. and Miele, L. and Geier, A. and Trautwein, C. and Aithal, G. and Hockings, P. and Newsome, P. and Wenn, D. and Rodrigues, C.M.P. and Chaumat, P. and Hanf, R. and Trylesinski, A. and Ortiz, P. and Duffin, K. and Brosnan, J. and Tuthill, T. and McLeod, E. and Ertle, J. and Younes, R. and Ostroff, R. and Alexander, L. and Kjær, M.S. and Mikkelsen, L.F. and Balp, M.-M. and Brass, C. and Jennings, L. and Martic, M. and Loeffler, J. and Hanauer, G. and Shankar, S. and Fournier, C. and Pepin, K. and Ehman, R. and Myers, J. and Ho, G. and Torstenson, R. and Myers, R. and Doward, L. and LITMUS Investigators",
    journal = "Gut Pathogens",
    year = "2021",
    publisher = "BMJ Publishing Group",
    issn = "1757-4749",
    doi = "10.1136/gutjnl-2021-324243",
    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 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. 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. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ."
}