Urinary Gas Chromatography‐Based Metabolomics for Early Detection of Liver Cirrhosis and Hepatocellular Carcinoma: A Decade of Progress

Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) represent major global health burdens. It is urgent to develop reliable and non-invasive testing technologies that can detect HCC early. The progress of urine metabolomics research has been exponential in the past decade (2016-2026). The method of analyzing volatile organic compounds (VOCs) provides more effective profiles than the traditional analysis of polar metabolites. As an example, in the earliest studies of gas chromatography-mass spectrometry (GC-MS) analysis, researchers identified several organic acids capable of differentiating healthy subjects from individuals with HCC. Despite these advances, distinguishing between cirrhosis and HCC remains challenging, delaying patient management and complicating urgent clinical decisions. New high-resolution analytical techniques such as gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) and gas chromatography-ion mobility spectrometry (GC-IMS) make the detection of minute quantities of aromatic compounds, ketones, and aldehydes much more manageable. The TENDENCY study was designed to evaluate these technologies within a large multicenter framework; however, outcome data have not yet been published. Overall, recent evidence suggests that urine metabolomics may represent a superior approach compared to invasive methods for earlier detection of hepatic disorder because the markers enable scientists to build up a "liquid biopsy" model.