Hepatitis C virus can induce gene expression changes associated with hepatocarcinogenesis.

Area of Science:

• Hepatology
• Oncology
• Virology
• Genomics

Background:

• Hepatitis C virus (HCV) is linked to liver cancer, primarily through chronic inflammation and regeneration.
• In vitro studies suggest HCV may have direct oncogenic effects, but human data is limited.

Purpose of the Study:

• To investigate whether HCV directly contributes to hepatocarcinogenesis in human liver tissues.
• To identify molecular mechanisms of HCV-induced liver cancer beyond inflammation.

Main Methods:

• A nested case-control study using a liver biopsy biobank.
• Propensity score matching of chronic hepatitis C patients who developed hepatocellular carcinoma (HCC) with controls without HCC.
• RNA and whole-exome sequencing of liver biopsies, followed by transcriptomic analysis and predictive model construction.

Main Results:

• Transcriptomic data significantly separated HCC cases from controls.
• Dysregulation of MYC target genes, unfolded protein response, and oxidative phosphorylation observed in HCC samples.
• A 19-gene signature identified as predictive of HCC risk, showing persistent molecular changes years before diagnosis.

Conclusions:

• HCV directly contributes to liver cancer through long-lasting, intrinsic molecular reprogramming of hepatocytes.
• Findings provide direct evidence for direct oncogenic mechanisms of HCV in humans.
• Transcriptomic signatures can predict HCC risk, aiding surveillance and prevention.