Metabolic dysfunction and cancer in HCV: Shared pathways and mutual interactions

Area of Science:

• Hepatology
• Virology
• Metabolic Medicine

Background:

• Hepatitis C virus (HCV) significantly alters host hepatic and systemic metabolism.
• Metabolic dysfunction, including obesity, insulin resistance, and hepatic steatosis, is a key factor in chronic hepatitis C (CHC) progression to hepatocellular carcinoma (HCC).
• Direct-acting antivirals (DAAs) have revolutionized CHC treatment, leading to viral eradication.

Purpose of the Study:

• To review the mechanisms by which HCV manipulates host metabolism.
• To highlight the role of metabolic disturbances in CHC progression and HCC development.
• To discuss the implications of persistent metabolic dysfunction post-DAA therapy.

Main Methods:

• Literature review of studies on HCV, host metabolism, and CHC natural history.
• Analysis of mechanisms linking viral infection, metabolic dysregulation, and liver disease.
• Examination of therapeutic strategies and outcomes in the context of metabolic dysfunction.

Main Results:

• HCV infection hijacks host metabolic processes, contributing to hepatic dysfunction and disease manifestations.
• Obesity, insulin resistance, and steatosis accelerate CHC progression and HCC risk.
• Sustained virologic response via DAAs may not resolve underlying metabolic issues, posing risks for liver disease progression and HCC.

Conclusions:

• HCV-induced metabolic alterations create a pro-inflammatory, lipotoxic environment that favors disease progression and oncogenesis.
• Persistent metabolic dysfunction after viral clearance is a significant concern, increasing the risk of liver disease progression and HCC.
• Management strategies must address both viral eradication and underlying metabolic comorbidities in CHC patients.