Disease-related effects on hepatic metabolism can alter the composition of chemicals in the circulation and subsequently in breath. The presence of disease related alterations in exhaled volatile organic compounds could therefore provide a basis for non-invasive biomarkers of hepatic disease. This study examined the feasibility of using global volatolomic profiles from breath analysis in combination with supervised machine learning to develop signature pattern-based biomarkers for cirrhosis. Breath samples were analyzed using thermal desorption-gas chromatography-field asymmetric ion mobility spectroscopy to generate breathomic profiles. A standardized collection protocol and analysis pipeline was used to collect samples from 35 persons with cirrhosis, 4 with non-cirrhotic portal hypertension, and 11 healthy participants. Molecular features of interest were identified to determine their ability to classify cirrhosis or portal hypertension. A molecular feature score was derived that increased with the stage of cirrhosis and had an AUC of 0.78 for detection. Chromatographic breath profiles were utilized to generate machine learning-based classifiers. Algorithmic models could discriminate presence or stage of cirrhosis with a sensitivity of 88-92% and specificity of 75%. These results demonstrate the feasibility of volatolomic profiling to classify clinical phenotypes using global breath output. These studies will pave the way for the development of non-invasive biomarkers of liver disease based on volatolomic signatures found in breath.
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