Accurate non-invasive diagnosis and staging of non-alcoholic fatty liver disease using the urinary steroid metabolome

Ahmad Moolla, Jasper de Boer, David Pavlov, Amin Amin, Angela Taylor, Lorna Gilligan, Beverly Hughes, John Ryan, Eleanor Barnes, Zaki Hassan-Smith, Jane Grove, Guruprasad P Aithal, An Verrijken, Sven Francque, Luc Van Gaal, Matthew J Armstrong, Phillip N Newsome, Jeremy F Cobbold, Wiebke Arlt, Michael BiehlJeremy W Tomlinson

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Abstract

BACKGROUND: The development of accurate, non-invasive markers to diagnose and stage non-alcoholic fatty liver disease (NAFLD) is critical to reduce the need for an invasive liver biopsy and to identify patients who are at the highest risk of hepatic and cardio-metabolic complications. Disruption of steroid hormone metabolic pathways has been described in patients with NAFLD.

AIM(S): To assess the hypothesis that assessment of the urinary steroid metabolome may provide a novel, non-invasive biomarker strategy to stage NAFLD.

METHODS: We analysed the urinary steroid metabolome in 275 subjects (121 with biopsy-proven NAFLD, 48 with alcohol-related cirrhosis and 106 controls), using gas chromatography-mass spectrometry (GC-MS) coupled with machine learning-based Generalised Matrix Learning Vector Quantisation (GMLVQ) analysis.

RESULTS: Generalised Matrix Learning Vector Quantisation analysis achieved excellent separation of early (F0-F2) from advanced (F3-F4) fibrosis (AUC receiver operating characteristics [ROC]: 0.92 [0.91-0.94]). Furthermore, there was near perfect separation of controls from patients with advanced fibrotic NAFLD (AUC ROC = 0.99 [0.98-0.99]) and from those with NAFLD cirrhosis (AUC ROC = 1.0 [1.0-1.0]). This approach was also able to distinguish patients with NAFLD cirrhosis from those with alcohol-related cirrhosis (AUC ROC = 0.83 [0.81-0.85]).

CONCLUSIONS: Unbiased GMLVQ analysis of the urinary steroid metabolome offers excellent potential as a non-invasive biomarker approach to stage NAFLD fibrosis as well as to screen for NAFLD. A highly sensitive and specific urinary biomarker is likely to have clinical utility both in secondary care and in the broader general population within primary care and could significantly decrease the need for liver biopsy.

Original languageEnglish
Pages (from-to)1188-1197
Number of pages10
JournalAlimentary Pharmacology & Therapeutics
Volume51
Issue number11
Early online date16-Apr-2020
DOIs
Publication statusPublished - Jun-2020

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