Breath Biopsy<sup>®</sup> 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 Snowdon
Abstract
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.