The potential of Volatile Organic Compounds to diagnose Primary Sclerosing Cholangitis

Introduction Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. PSC is a complex disease of largely unknown aetiology with a strong association with inflammatory bowel disease (IBD). Diagnosis, especially at early stage, is difficult and to date there is no diagnostic biomarker. The present study aimed to assess the diagnostic potential of Volatile Organic Compounds (VOCs) in exhaled breath to detect (early) PSC in an IBD population. Methods Breath samples were obtained from 16 PSC, 47 PSC with IBD, and 53 IBD patients during outpatient clinic visit. Breath sampling was performed using the ReCIVA breath sampler and subsequently analysed by gas chromatography mass spectrometry. Random Forest modelling was performed to find discriminatory VOCs and create a predictive model that was tested using an independent test set. Results The final model to discriminate PSC patients with or without IBD versus IBD only patients included twenty VOCs and achieved a sensitivity, specificity, and area under the receiver operating curve on the test set of 77%, 83%, and 0.84 respectively. Three VOCs (isoprene, 2-octanone and undecane) together correlated significantly to the Amsterdam-Oxford score for PSC disease prognosis. A sensitivity analysis showed stable results across early stage PSC including those with normal alkaline phosphatase levels, as well as further progressed PSC. Conclusion The present study demonstrates that exhaled breath can distinguish PSC cases from IBD and has potential as a non-invasive clinical breath test for (early) PSC. Impact and Implications Primary Sclerosing Cholangitis (PSC) is a complex chronic liver disease, which ultimately results in cirrhosis, liver failure, and death. Detection especially in early disease can be challenging, and therefore therapy typically starts when there is already some irreversible damage. The current study shows that metabolites in exhaled breath, so called Volatile Organic Compounds, hold promise to non-invasively detect PSC also at early stages.