Breath Biopsy^(®) to Identify Exhaled Volatile Organic Compounds Biomarkers for Liver Cirrhosis Detection

Background and Aims:The prevalence of chronic liver dis-ease 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 so-lutions suitable for early-stage detection and disease moni-toring.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 can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from controls.Collection and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(GC-MS).Blank samples were also analyzed to provide de-tailed 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 classifica-tion performance.A subset of 11 VOCs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin 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 mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.