Volatile organic compounds for diagnosis of early hepatocellular carcinoma in at-risk patients

•HCC surveillance with ultrasonography and serum AFP has a limited sensitivity for detecting early HCC in high-risk patients.•VOCs have been increasingly shown to have potential as cancer biomarkers.•In this study of 87 early HCC, 90 cirrhosis and 72 HBV-infected patients, VOCs were strongly associated with HCC.•VOCs outperformed AFP in discriminating early HCC patients from cirrhotic and HBV-infected patients.•Combining VOCs with ultrasonography and AFP could potentially offer a more effective approach to HCC surveillance. Volatile organic compounds (VOCs) have been 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. VOCs were identified in exhaled breath samples collected from 87 early-stage HCC patients, 90 cirrhotic patients, and 72 HBV-infected patients using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the three 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). The levels of acetone monomer, dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone dimer were significantly different between the three groups. After adjusting for liver function test and AFP, acetone dimer was significantly associated with HCC. Acetone dimer significantly outperformed AFP with 86.2 % vs. 61.2 % sensitivity, 87.6 % vs. 66.2 % specificity, 86.9 % vs. 63.5 % for accuracy, and AUROC of 0.908 vs. 0.665, p = 0.007,