Breath Biopsy® to Identify Exhaled Volatile Organic Compounds Biomarkers for Liver Cirrhosis Detection.

Giuseppe Ferrandino, Giovanna De Palo, Antonio Murgia, Owen Birch, Ahmed Tawfike, Rob Smith, Irene Debiram-Beecham, Olga Gandelman, Graham Kibble, Anne Marie Lydon, Alice Groves, Agnieszka Smolinska, Max Allsworth, Billy Boyle, Marc P van der Schee, Michael Allison, Rebecca C Fitzgerald, Matthew Hoare, Victoria K Snowdon

OAI: oai:www.repository.cam.ac.uk:1810/348855 • DOI: 10.17863/CAM.96281

BACKGROUND AND AIMS: The prevalence of chronic liver disease in adults exceeds 30% in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare burden. Breath is a rich sampling matrix that offers non-invasive solutions suitable for early-stage detection and disease monitoring. Having previously investigated targeted analysis of a single biomarker, here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical use. METHODS: To identify candidate biomarkers we compared 46 breath samples from cirrhosis patients and 42 from controls. Collection and analysis used Breath Biopsy OMNI™, maximizing signal and contrast to background to provide high confidence biomarker detection based upon gas chromatography mass spectrometry (GC-MS). Blank samples were also analyzed to provide detailed information on background volatile organic compounds (VOCs) levels. RESULTS: A set of 29 breath VOCs differed significantly between cirrhosis and controls. A classification model based on these VOCs had an area under the curve (AUC) of 0.95±0.04 in cross-validated test sets. The seven best performing VOCs were sufficient to maximize classification performance. A subset of 11 VOCs was correlated with blood metrics of liver function (bilirubin, albumin, prothrombin time) and separated patients by cirrhosis severity using principal component analysis. CONCLUSIONS: A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and monitoring, showing correlation to disease severity and serum biomarkers at late stage.

biomarker Breath Biopsy cirrhosis Liver function test non-invasive