Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study
David Sheridan,
Jeremy F Cobbold,
Jeremy W Tomlinson,
William Alazawi,
Richard Parker,
Alice J Sitch,
Fredrik Karpe,
David Harman,
Hamish Miller,
Márta Korbonits,
Philip N Newsome,
Guruprasad Padur Aithal,
Pinelopi Manousou,
Wiebke Arlt,
Matthew Neville,
Michael Biehl
Affiliations
David Sheridan
Institute of Translational and Stratified Medicine, University of Plymouth, Plymouth, UK
Jeremy F Cobbold
Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Jeremy W Tomlinson
Oxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
William Alazawi
Barts Liver Centre, Queen Mary University London and Barts Health NHS Trust, London, UK
Richard Parker
Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Alice J Sitch
National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK
Fredrik Karpe
Oxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
David Harman
Royal Berkshire Hospital NHS Foundation Trust, Reading, UK
Hamish Miller
Oxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
Márta Korbonits
Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Philip N Newsome
National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK
Guruprasad Padur Aithal
NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
Pinelopi Manousou
Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Wiebke Arlt
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Matthew Neville
Oxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
Michael Biehl
Faculty of Science and Engineering, Bernoulli Institute for Mathematics, Computer Science and Artificial Intelligence, University of Groningen, Groningen, Netherlands
Introduction Non-alcoholic fatty liver disease (NAFLD) affects approximately one in four individuals and its prevalence continues to rise. The advanced stages of NAFLD with significant liver fibrosis are associated with adverse morbidity and mortality outcomes. Currently, liver biopsy remains the ‘gold-standard’ approach to stage NAFLD severity. Although generally well tolerated, liver biopsies are associated with significant complications, are resource intensive, costly, and sample only a very small area of the liver as well as requiring day case admission to a secondary care setting. As a result, there is a significant unmet need to develop non-invasive biomarkers that can accurately stage NAFLD and limit the need for liver biopsy. The aim of this study is to validate the use of the urine steroid metabolome as a strategy to stage NAFLD severity and to compare its performance against other non-invasive NAFLD biomarkers.Methods and analysis The TrUSt-NAFLD study is a multicentre prospective test validation study aiming to recruit 310 patients with biopsy-proven and staged NAFLD across eight centres within the UK. 150 appropriately matched control patients without liver disease will be recruited through the Oxford Biobank. Blood and urine samples, alongside clinical data, will be collected from all participants. Urine samples will be analysed by liquid chromatography-tandem mass spectroscopy to quantify a panel of predefined steroid metabolites. A machine learning-based classifier, for example, Generalized Matrix Relevance Learning Vector Quantization that was trained on retrospective samples, will be applied to the prospective steroid metabolite data to determine its ability to identify those patients with advanced, as opposed to mild-moderate, liver fibrosis as a consequence of NAFLD.Ethics and dissemination Research ethical approval was granted by West Midlands, Black Country Research Ethics Committee (REC reference: 21/WM/0177). A substantial amendment (TrUSt-NAFLD-SA1) was approved on 26 November 2021.Trial registration number ISRCTN19370855.
