Profiling of plasma metabolomics in patients with hepatitis C-related liver cirrhosis and hepatocellular carcinoma

Aim of the study
The diagnosis of hepatocellular carcinoma (HCC) is usually late, due to the lack of early detection of biomarkers for HCC. Metabolomics analysis has emerged as a useful tool for studying human diseases. The objective of the study was to investigate the differences in plasma metabolites between hepatitis C virus (HCV)-induced cirrhosis and HCC.

Material and methods
22 subjects with HCV-related liver cirrhosis and 22 subjects with HCC were enrolled. Clinical, routine laboratory and imaging studies were done. Gas chromatography/mass spectrometry (GC/MS) was used for metabolomics analysis of patients’ plasma samples.

Results
34 known metabolites were detected, of which five metabolites were identified to have the strongest discriminatory power for separation between HCC and cirrhosis groups: octanoic acid (caprylic acid), decanoic (capric acid), oleic acid, oxalic acid and glycine. These are 3 fatty acids (FA), a dicarboxylic acid and a glucogenic amino acid, respectively. No significant correlation was found between the relative intensities of the five metabolites and any of the patient or tumor characteristics (Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, number of focal lesions and size of largest focal lesion). ROC curve analysis was performed and area under the curve (AUC) was calculated, revealing that oleic acid, octanoic (caprylic) acid and glycine had higher positive predictive value than α-fetoprotein.

Conclusions
The study of metabolomics (particularly involving FA) may help define distinct metabolic patterns to distinguish HCV-induced liver cirrhosis from HCC patients. Future research in this field is still needed, particularly concerning HCC treatment strategies which target fatty acid-related metabolic pathways.