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

  • Mózes, Ferenc Emil1
  • Lee, Jenny A2
  • Selvaraj, Emmanuel Anandraj1, 3, 4
  • Jayaswal, Arjun Narayan Ajmer1
  • Trauner, Michael5
  • Boursier, Jerome6, 7
  • Fournier, Céline8
  • Staufer, Katharina5, 9, 10
  • Stauber, Rudolf E11
  • Bugianesi, Elisabetta12
  • Younes, Ramy13
  • Gaia, Silvia12
  • Lupșor-Platon, Monica14
  • Petta, Salvatore15
  • Shima, Toshihide16
  • Okanoue, Takeshi16
  • Mahadeva, Sanjiv17
  • Chan, Wah-Kheong17
  • Eddowes, Peter J18, 19
  • Newsome, Philip Noel18, 20, 21
  • And 32 more
  • 1 Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • 2 Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. , (Netherlands)
  • 3 Translational Gastroenterology Unit, University of Oxford, Oxford, Oxfordshire, UK.
  • 4 NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK.
  • 5 Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. , (Austria)
  • 6 Laboratoire HIFIH, UPRES EA 3859, SFR ICAT 4208, Universite d'Angers, Angers, Pays de la Loire, France. , (France)
  • 7 Service d'Hepato-Gastroenterologie et Oncologie Digestive, Centre Hospitalier Universitaire d'Angers, Angers, Pays de la Loire, France. , (France)
  • 8 Echosens SA, Paris, Île-de-France, France. , (France)
  • 9 Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, Bern, Switzerland. , (Switzerland)
  • 10 Department of Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria. , (Austria)
  • 11 Department of Internal Medicine, Medical University of Graz, Graz, Austria. , (Austria)
  • 12 Medical Sciences, University of Turin, Torino, Italy. , (Italy)
  • 13 Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany. , (Germany)
  • 14 Department of Ultrasonography, University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj Napoca, Romania. , (Oman)
  • 15 Section of Gastroenterology and Hepatology, PROMISE, Palermo, Italy. , (Italy)
  • 16 Hepatology Center, Saiseikai Suita Hospital, Suita, Osaka, Japan. , (Japan)
  • 17 Faculty of Medicine, Department of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia. , (Malaysia)
  • 18 NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK.
  • 19 NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, Nottinghamshire, UK.
  • 20 Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • 21 Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • 22 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong. , (Hong Kong SAR China)
  • 23 Centre d'Investigation de la Fibrose Hépatique, Hopital Haut-Leveque, Pessac, France. , (France)
  • 24 INSERM1053, Universite de Bordeaux, Talence, Aquitaine, France. , (France)
  • 25 Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. , (China)
  • 26 Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi, Japan. , (Japan)
  • 27 Department of Gastroenterology, Koseikai Takeda Hospital, Kyoto, Japan. , (Japan)
  • 28 Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Rhineland-Palatinate, Germany. , (Germany)
  • 29 Department of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea. , (North Korea)
  • 30 Department of Radiology, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, The Republic of Korea. , (North Korea)
  • 31 Department of Medicine II, Leipzig University Medical Center, Leipzig, Sachsen, Germany. , (Germany)
  • 32 Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey. , (Turkey)
  • 33 Institute of Gastroenterology, Marmara University, Istanbul, Turkey. , (Turkey)
  • 34 Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.
  • 35 Diagnostic and Interventional Radiology, University Hospital Centre Montpellier, Montpellier, Languedoc-Roussillon, France. , (France)
  • 36 Department of Surgical Disciplines, AIIMS, New Delhi, Delhi, India. , (India)
  • 37 Department of Surgery, Monash University, Prahran, Victoria, Australia. , (Australia)
  • 38 Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Kanagawa, Japan. , (Japan)
  • 39 Service d'Anatomie Pathologique et Centre de Ressources Biologiques, Hopital Jean Verdier, Paris, France. , (France)
  • 40 Centre de Ressources Biologiques, Hopitaux Universitaires Paris-Seine-Saint-Denis, Bondy, Île-de-France, France. , (France)
  • 41 Division of Hepatology, University Hospital Wurzburg, Wurzburg, Bayern, Germany. , (Germany)
  • 42 Internal Medicine Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA.
  • 43 Translational and Clinical Research Institute, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.
  • 44 Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK [email protected]
Published Article
Publication Date
May 17, 2021
DOI: 10.1136/gutjnl-2021-324243
PMID: 34001645


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. © 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.

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