Long-chain acylcarnitine deficiency promotes hepatocarcinogenesis

Area of Science:

• Hepatology
• Metabolomics
• Oncology

Background:

• Chronic hepatitis B (CHB) patients on antiviral therapy still face a high risk of hepatocellular carcinoma (HCC).
• Metabolites are increasingly recognized as key players in carcinogenesis, but their specific role in CHB-associated HCC remains unclear.

Purpose of the Study:

• To identify specific metabolites associated with HCC development in CHB patients.
• To investigate the functional role of identified metabolites in HCC prevention and their underlying molecular mechanisms.

Main Methods:

• Prospective cohort study with nested case-control design.
• Plasma metabolomics analysis.
• In vitro and in vivo experiments using HCC cell lines and animal models.

Main Results:

• Baseline plasma from CHB patients who developed HCC showed growth-promoting properties.
• Reduced levels of long-chain acylcarnitines (LCACs) were observed in patients who developed HCC.
• LCACs inhibited HCC cell proliferation in vitro, prevented HCC in vivo, and acted via the KLF6/p21 pathway.

Conclusions:

• Deficiency in circulating LCACs is a potential driver of HCC in CHB patients with controlled viral replication.
• LCACs represent a promising therapeutic target for reducing HCC risk in the antiviral era.