Volatile Organic Compounds for the Detection of Hepatocellular Carcinoma: a Systematic Review

BackgroundHepatocellular carcinoma (HCC) is an increasingly common and one of the leading causes of cancer mortality worldwide. Only a small percentage of HCC patients are eligible to curative treatment. There is a need for a point of care, early diagnostic or screening tool. It is not clear whether exhaled volatile organic compounds (VOCs) could fulfil those needs. HypothesisWe postulate that exhaled VOCs can identify potential biomarkers for non-invasive detection of HCC. AimsThis systematic review aims to critically review the current knowledge regarding the exhaled VOCs linked to HCC detection. MethodsA systematic electronic search was conducted. Search strategy included all studied published until the 24th of March 2021 using a combination of relevant keywords. ResultsThe search yielded 6 publications using the PRISMA pathway. Two of the studies described in vitro experiments, and four clinical studies were conducted on small groups of patients. Overall, 42 headspace gases were analysed in the in vitro studies. Combined, the clinical studies included 164 HCC patients and 260 controls. The studies reported potential role for a combination of VOCs in the diagnosis of HCC. However, only limonene, acetaldehyde and ethanol could be traced back to their biological pathways using KEGG pathway enrichment analysis. ConclusionsAlthough there appears to be promise in VOCs research associated with HCC, there is no single volatile biomarker in exhaled breath attributed to HCC and data from extracted studies indicates a lack of standardization. Large population studies are required to verify the existence of VOCs linked to HCC.