Analysis of VOCs from exhaled breath for the diagnosis of hepatocellular carcinoma

Abstract

Background: Volatile organic compounds (VOCs) were shown as promising biomarkers for hepatocellular carcinoma (HCC) diagnosis. We aimed to investigate the performance of VOCs for diagnosing early-stage HCC in patients at-risk for HCC.

Methods: VOCs were identified in exhaled breath samples collected from 90 early-stage HCC patients, 90 cirrhotic patients, 91 HBV-infected patients, and 95 healthy volunteers using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the four groups. An association between VOCs and HCC was determined using logistic regression analysis. Diagnostic performance of VOCs was estimated using the AUROC and compared to serum alpha-fetoprotein (AFP).

Results: The levels of dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone were significantly different between the four groups. After adjusting for liver function test and AFP, acetone was significantly associated with HCC. Acetone significantly outperformed AFP, with 88.9% vs. 68.2% sensitivity, 87.3% vs. 63.6% specificity, 87.7% vs. 65.2% for accuracy, and AUROC of 0.932 vs. 0.725, p=0.017, 0.001, <0.001, and 0.001, respectively, for differentiating between HCC and non-HCC group.

Conclusion: Acetone has a better performance than AFP for diagnosing early HCC in high-risk patients. Further studies to validate the utility of VOCs as a HCC surveillance tool are needed.