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

Mózes FE 1 , Lee JA 2 , Selvaraj EA 1 , Jayaswal ANA 1 , Trauner M 3 , Boursier J 4 Show all authors , Fournier C 5 , Staufer K 3 , Stauber RE 6 , Bugianesi E 7 , Younes R 8 , Gaia S 7 , Lupșor-Platon M 9 , Petta S 10 , Shima T 11 , Okanoue T 11 , Mahadeva S 12 , Chan WK 12 , Eddowes PJ 13 , Hirschfield GM 14 , Newsome PN 13 , Wong VW 15 , de Ledinghen V 16 , Fan J 17 , Shen F 17 , Cobbold JF 18 , Sumida Y 19 , Okajima A 20 , Schattenberg JM 21 , Labenz C 21 , Kim W 22 , Lee MS 23 , Wiegand J 24 , Karlas T 24 , Yılmaz Y 25 , Aithal GP 26 , Palaniyappan N 26 , Cassinotto C 27 , Aggarwal S 28 , Garg H 28 , Ooi GJ 29 , Nakajima A 30 , Yoneda M 30 , Ziol M 31 , Barget N 32 , Geier A 33 , Tuthill T 34 , Brosnan MJ 34 , Anstee QM 35 , Neubauer S 1 , Harrison SA 1 , Bossuyt PM 2 , Pavlides M 36 , LITMUS Investigators

Affiliations 

  • 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
  • 3 Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
  • 4 Laboratoire HIFIH, UPRES EA 3859, SFR ICAT 4208, Universite d'Angers, Angers, Pays de la Loire, France
  • 5 Echosens SA, Paris, Île-de-France, France
  • 6 Department of Internal Medicine, Medical University of Graz, Graz, Austria
  • 7 Medical Sciences, University of Turin, Torino, Italy
  • 8 Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • 9 Department of Ultrasonography, University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj Napoca, Romania
  • 10 Section of Gastroenterology and Hepatology, PROMISE, Palermo, Italy
  • 11 Hepatology Center, Saiseikai Suita Hospital, Suita, Osaka, Japan
  • 12 Faculty of Medicine, Department of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
  • 13 NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK
  • 14 Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
  • 15 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong
  • 16 Centre d'Investigation de la Fibrose Hépatique, Hopital Haut-Leveque, Pessac, France
  • 17 Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 18 Translational Gastroenterology Unit, University of Oxford, Oxford, Oxfordshire, UK
  • 19 Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi, Japan
  • 20 Department of Gastroenterology, Koseikai Takeda Hospital, Kyoto, Japan
  • 21 Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Rhineland-Palatinate, Germany
  • 22 Department of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea
  • 23 Department of Radiology, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Dongjak-gu, Seoul, The Republic of Korea
  • 24 Department of Medicine II, Leipzig University Medical Center, Leipzig, Sachsen, Germany
  • 25 Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey
  • 26 NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, Nottinghamshire, UK
  • 27 Diagnostic and Interventional Radiology, University Hospital Centre Montpellier, Montpellier, Languedoc-Roussillon, France
  • 28 Department of Surgical Disciplines, AIIMS, New Delhi, Delhi, India
  • 29 Department of Surgery, Monash University, Prahran, Victoria, Australia
  • 30 Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Kanagawa, Japan
  • 31 Service d'Anatomie Pathologique et Centre de Ressources Biologiques, Hopital Jean Verdier, Paris, France
  • 32 Centre de Ressources Biologiques, Hopitaux Universitaires Paris-Seine-Saint-Denis, Bondy, Île-de-France, France
  • 33 Division of Hepatology, University Hospital Wurzburg, Wurzburg, Bayern, Germany
  • 34 Internal Medicine Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA
  • 35 Translational and Clinical Research Institute, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
  • 36 Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK michael.pavlides@cardiov.ox.ac.uk
Gut, 2021 May 17.
PMID: 34001645 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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