Author information
1Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK. Electronic address: Michael.pavlides@cardiov.ox.ac.uk.
2Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
3Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
4Translational Gastroenterology Unit, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK.
5Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK.
6Liver Unit, Department of Medicine, Cambridge NIHR Biomedical Research Centre, Cambridge University NHS Foundation Trust, UK.
7Department of Radiology, Cambridge University NHS Foundation Trust, Cambridge, UK.
8NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.
9Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK.
10Digestive Diseases Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
11Radiodiagnosis Clinical Management Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
12Department of Gastroenterology, Clinic University Hospital, Medical School, University of Valladolid, CIBERINFEC, Valladolid, Spain.
13Department of Radiology, Clinic University Hospital, Medical School, University of Valladolid, Valladolid, Spain.
14Liver Unit, Vall d'Hebron Institut de Recerca, Vall d'Hebron Barcelona Hospital, Centros de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
15Centre Hospitalier Universitaire d'Angers, Angers, France; & Laboratoire HIFIH UPRES EA3859, Université d'Angers, Angers, France.
16Department of Radiology, Centre Hospitalier Universitaire d'Angers, Angers, France; & Laboratoire HIFIH UPRES EA3859, Université d'Angers, Angers, France.
17Sorbonne Université, Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.
18Radiology department, AP-HP.6, GH Pitié Salpêtrière - Charles Foix Sorbonne Université, Paris, France.
19Section of Gastroenterology, PROMISE, University of Palermo, Italy.
20Section of Radiology - Di.Bi.Me.F., University of Palermo, Palermo, Italy.
21Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy.
22Department of Diagnostic and Interventional Radiology, University of Turin, Turin, Italy.
23Department of Translational Medicine and Surgery, Medical School, Università Cattolica del S. Cuore and Fondazione Pol. Gemelli IRCCS Hospital, Rome, Italy.
24Department of Hepatology, University of Würzburg, Würzburg, Germany.
25Metabolic Liver Research Program, I. Department of Medicine, University Medical Centre, Mainz, Germany.
26Department of Diagnostic and Interventional Radiology, University Medical Center of Johannes-Gutenberg-University, Langenbeckstr. 1, 55131 Mainz, Germany.
27Department of Health, Medicine and Caring Sciences, and Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
28Department of Radiation Physics, and Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
29Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
30Department of Diagnostic, Interventional and Paediatric Radiology (DIPR), Bern University Hospital, University of Bern, Bern, Switzerland.
31Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
32Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
33Antaros Medical AB, Mölndal, Sweden.
34Perspectum Ltd, Oxford, UK.
35Resoundant Inc, Rochester, MN, USA.
36Department of Radiology, Mayo Clinic, Rochester, MN, USA.
37ADVANZPHARMA, Capital House, 1st Floor, 85 King William Street, London EC4N 7BL, United Kingdom.
38Boehringer Ingelheim Pharma GmbH & Co., KG, Germany.
39Novartis AG, Translational Medicine, Clinical and Precision Medicine Imaging, Basel, Switzerland.
40Clinical Development and Operations, Pfizer Inc., Lake Mary, FL, USA.
41Department of Epidemiology & Data Science, Amsterdam Public Health, Amsterdam University Medical Centres, University of Amsterdam, the Netherlands.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.