Investigating the breath metabolome as a diagnostic tool for hepatocellular carcinoma in cirrhotic patients

Abstract

Background: Non-invasive diagnostic testing for hepatocellular carcinoma in cirrhotic patients is attractive since cirrhotic patients often exhibit marginal renal function and coagulopathy which complicates their ability to undergo imaging with contrast medium and/or needle biopsy. Selective ion flow tube mass spectrometry (SIFT-MS) is a non-invasive test that can be used to identify trace gases in human breath. This study investigated the level of volatile organic compounds (VOCs) in cirrhosis patients and evaluated the difference of VOCs according to the presence of hepatocellular carcinoma (HCC). Methods: Cirrhotic patients without HCC (n = 22) and with HCC (n = 57) were included in this study. Cirrhosis and HCC were diagnosed based on imaging studies or biopsy. Clinical characteristics were compared between the groups using Fisher's exact and the Mann–Whitney test. Analysis of covariance (ANCOVA) was used to estimate age and gender adjusted average VOC levels between the two groups. Receiver operating characteristic (ROC) analysis was performed to assess discriminatory ability of VOCs. Results: Baseline characteristics were similar between the groups. Median age was significantly higher in HCC group (67 yo vs 58 yo, p < 0.001). In ANCOVA analysis, the mean breath concentrations of 3 VOCs (acetone, isoprene and pentane) were significantly lower in HCC group (all p < 0.05). The ROC analyses were performed in those 3 VOCs and an area under the curve of acetone, isoprene and pentane were 0.841 (95%CI: 0.752–0.929), 0.789 (95%CI: 0.691, 0.886), and 0.828 (95%CI: 0.734–0.922), respectively. Conclusion: Breath metabolome analysis could be a potential non-invasive diagnostic tool for HCC in cirrhotic patients. This observation warrants further investigation in larger cohorts.