Metabolomic comparative study in patients with liver cirrhosis and hepatocellular carcinoma related to hepatitis B virus infection.

Abstract

Introduction: Chronic hepatitis B virus (HBV) infection can increase the risk of developing liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Timely detection of precancerous lesions for patients with chronic HBV infection is critical in preventing worse consequences. The purpose of this study is to reveal the key serum metabolic biomarkers that can be applied to the early recognition of HCC in patients with HBV-associated cirrhosis.

Methods: Blood samples from patients with LC, HCC, and healthy subjects were collected, and endogenous metabolites in serum were detected by ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Differential metabolites (DM) were screened, and metabolic pathways and Kyoto Encyclopedia of Genes and Genomes signals involved in DM were analyzed.

Results: Metabolomics results revealed that patients with LC and HCC had significantly different metabolic characteristics. Patients with LC and HCC shared 22 biomarkers, LC had six different biomarkers, and HCC had 10 different biomarkers. The expressions of these metabolites all showed significant differences between groups. Pathway enrichment analysis revealed that the differential biomarkers of LC were primarily involved in the regulation of phospholipid biosynthesis, while the differential biomarkers of HCC were mainly involved in the regulation of endogenous androgen signaling, mitochondrial fatty acid metabolism, and purine metabolism signaling. The common biomarkers are enriched in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism.

Conclusion: We clarified the blood metabolism characteristics of LC and HCC. These findings provided potential endogenous metabolic indicators for early recognition of HBV-chronically infected cirrhotic patients who may progress to HCC.