Skip to main content

Research Repository

Advanced Search

Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study.

Miller, Hamish; Harman, David; Aithal, Guruprasad Padur; Manousou, Pinelopi; Cobbold, Jeremy F; Parker, Richard; Sheridan, David; Newsome, Philip N; Karpe, Fredrik; Neville, Matthew; Arlt, Wiebke; Sitch, Alice J; Korbonits, Marta; Biehl, Michael; Alazawi, William; Tomlinson, Jeremy W

Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study. Thumbnail


Authors

Hamish Miller

David Harman

Pinelopi Manousou

Jeremy F Cobbold

Richard Parker

David Sheridan

Philip N Newsome

Fredrik Karpe

Matthew Neville

Wiebke Arlt

Alice J Sitch

Marta Korbonits

Michael Biehl

William Alazawi

Jeremy W Tomlinson



Abstract

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.

Citation

Miller, H., Harman, D., Aithal, G. P., Manousou, P., Cobbold, J. F., Parker, R., …Tomlinson, J. W. (2024). Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study. BMJ Open, 14(1), Article e074918. https://doi.org/10.1136/bmjopen-2023-074918

Journal Article Type Article
Acceptance Date Jan 9, 2024
Online Publication Date Jan 18, 2024
Publication Date Jan 18, 2024
Deposit Date Jan 23, 2024
Publicly Available Date Jan 25, 2024
Journal BMJ Open
Electronic ISSN 2044-6055
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 14
Issue 1
Article Number e074918
DOI https://doi.org/10.1136/bmjopen-2023-074918
Keywords Hepatology, Diabetes & Endocrinology, General Endocrinology, Liver, Humans, Liver Cirrhosis, Steroids, Biopsy, Retrospective Studies, Trust, Multicenter Studies as Topic, Metabolome, Non-alcoholic Fatty Liver Disease, Biomarkers
Public URL https://nottingham-repository.worktribe.com/output/30111660
Publisher URL https://bmjopen.bmj.com/content/14/1/e074918
PMID 38238179

Files

Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study. (338 Kb)
PDF

Copyright Statement
cc by


Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study. (341 Kb)
PDF

Copyright Statement
cc by






You might also like



Downloadable Citations