Volatomic analysis identifies compounds that can stratify non-alcoholic fatty liver disease

JHEP Reports

Khalida A. Lockman¹  Edward Bower²  Peter C. Hayes³  Jonathan A. Fallowfield⁴  Natalie Z.M. Homer⁵  John N. Plevris⁶  Alan J. Jaap⁷  Rohit Sinha⁸  Hugo H. Knobel⁹  Paul Brinkman⁹ 

[1] Corresponding author: Address: Liver Unit, The Royal Infirmary and The University of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK. Tel.: [phone], fax: [phone].;General Medicine, Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, UK;Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK;Department of Respiratory Medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands;;Edinburgh Acute &Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, UK;Eurofins Materials Science Netherlands BV, High Tech Campus, Eindhoven, The Netherlands;Hepatology Laboratory and Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, UK;Mass Spectrometry Core, Edinburgh Clinical Research Facility, Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK;

关键词: Volatile organic compounds;    Non-alcoholic fatty liver disease;    Volatomics;    Terpinene;    D-limonene;    Dimethyl sulfide;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background & aims: Analysis of volatile organic compounds (VOCs) in exhaled breath, ‘volatomics’, provides opportunities for non-invasive biomarker discovery and novel mechanistic insights into a variety of diseases. The purpose of this pilot study was to compare breath VOCs in an initial cohort of patients with non-alcoholic fatty liver disease (NAFLD) and healthy controls. Methods: Breath samples were collected from 15 participants with Child-Pugh class A NAFLD cirrhosis, 14 with non-cirrhotic NAFLD, and 14 healthy volunteers. Exhaled breath samples were collected using an established methodology and VOC profiles were analysed by gas chromatography-mass spectrometry. The levels of 19 VOCs previously associated with cirrhosis were assessed. Peaks of the VOCs were confirmed and integrated using Xcalibur® software, normalised to an internal standard. Receiver-operating characteristic (ROC) curves were used to determine the diagnostic accuracy of the candidate VOCs. Results: Terpinene, dimethyl sulfide, and D-limonene provided the highest predictive accuracy to discriminate between study groups. Combining dimethyl sulfide with D-limonene led to even better discrimination of patients with NAFLD cirrhosis from healthy volunteers (AUROC 0.98; 95% CI 0.93–1.00; p <0.001) and patients with NAFLD cirrhosis from those with non-cirrhotic NAFLD (AUROC 0.91; 95% CI 0.82–1.00; p <0.001). Breath terpinene concentrations discriminated between patients with non-cirrhotic NAFLD and healthy volunteers (AUROC 0.84; 95% CI 0.68–0.99; p = 0.002). Conclusion: Breath terpinene, dimethyl sulfide, and D-limonene are potentially useful volatomic markers for stratifying NAFLD; in addition, a 2-stage approach enables the differentiation of patients with cirrhosis from those without. However, these observations require validation in a larger NAFLD population. (ClinicalTrials.gov Identifier: NCT02950610). Lay summary: Breath malodour has been associated with a failing liver since the ancient Greeks. Analytical chemistry has provided us an insight into ubiquitous volatile organic compounds associated with liver (and other) diseases. This has vastly improved our understanding of the mechanistic processes of liver damage. Our study aims to identify volatile organic compounds which are specific to non-alcoholic fatty liver disease and that can be exploited for rapid diagnostics.

【 授权许可】

Unknown