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

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

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.

Aim(s): As the liver represents the main site of steroid hormone metabolism, and disruption of specific pathways has been described in patients with NAFLD, we hypothesised 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, 106 controls), using gas chromatography-mass spectrometry (GC-MS) coupled with machine learning-based generalised matrix learning vector quantisation (GMLVQ) analysis.

Results: GMLVQ analysis achieved excellent separation of early (F0-F2) from advanced (F3-F4) fibrosis (AUC 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.

Citation

Moolla, A., de Boer, J., Pavlov, D., Amin, A., Taylor, A., Gilligan, L., Hughes, B., Ryan, J., Barnes, E., Hassan-Smith, Z., Grove, J., Aithal, G. P., Verrijken, A., Francque, S., Van Gaal, L., Armstrong, M. J., Newsome, P. N., Cobbold, J. F., Arlt, W., Biehl, M., & Tomlinson, J. W. (2020). Accurate non-invasive diagnosis and staging of non-alcoholic fatty liver disease using the urinary steroid metabolome. Alimentary Pharmacology and Therapeutics, 51(11), 1188-1197. https://doi.org/10.1111/apt.15710

• Journal Article Type: Article
• Acceptance Date: Mar 15, 2020
• Online Publication Date: Apr 16, 2020
• Publication Date: 2020-06
• Deposit Date: Apr 16, 2020
• Publicly Available Date: Apr 21, 2020
• Journal: Alimentary Pharmacology and Therapeutics
• Print ISSN: 0269-2813
• Electronic ISSN: 1365-2036
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 51
• Issue: 11
• Pages: 1188-1197
• DOI: https://doi.org/10.1111/apt.15710
• Keywords: Non-alcoholic fatty liver disease, NAFLD, steroid, urine, pharmacology (medical)
• Public URL: https://nottingham-repository.worktribe.com/output/4297467
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/apt.15710