Rewiring Host Signaling: Hepatitis C Virus in Liver Pathogenesis

Area of Science:

• Hepatology
• Virology
• Oncology

Background:

• Hepatitis C virus (HCV) infection is a primary driver of liver diseases, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC).
• Direct-acting antivirals (DAAs) achieve high cure rates for HCV, but HCC risk persists, particularly in patients with advanced liver disease or comorbidities.
• HCV establishes a persistent epigenetic viral footprint, promoting a pro-oncogenic hepatic signature even after viral eradication.

Purpose of the Study:

• To review signaling pathways deregulated by HCV infection and their impact on liver pathogenesis.
• To explore the potential of persistent HCV-induced signaling patterns as biomarkers for HCC risk stratification in cured patients.
• To identify these signaling pathways as potential targets for novel chemopreventive strategies.

Main Methods:

• This review synthesizes current research on HCV-induced signaling pathways.
• Analysis of literature focusing on the epigenetic impact of HCV on liver cells.
• Examination of studies investigating post-cure HCC risk and potential biomarkers.

Main Results:

• HCV infection deregulates critical survival, proliferative, and metabolic pathways within the liver.
• An epigenetic viral footprint persists post-HCV cure, contributing to a pro-oncogenic hepatic environment.
• Persistent signaling patterns are implicated in ongoing liver pathogenesis and HCC development.

Conclusions:

• Despite successful HCV eradication with DAAs, the risk of HCC remains due to persistent viral-induced signaling.
• Persistent HCV-induced signaling pathways may serve as valuable biomarkers for identifying high-risk patients.
• Targeting these persistent pathways offers a promising avenue for developing chemopreventive therapies against HCC in HCV-cured individuals.