Hepatocellular carcinoma (HCC) developing in the context of chronic hepatitis C infection is primarily attributable to which mechanism?

• A Direct viral insertional mutagenesis by HCV integrating into cellular oncogene promoters
• B HCV core protein directly activating Wnt-β-catenin signalling independent of cirrhosis
• C Cirrhosis-mediated regenerative hyperplasia driving accumulated genetic mutations in hepatocytes ✓
• D Immune-mediated polyclonal B cell activation producing hepatocyte-reactive autoantibodies

Explanation

Unlike HBV, hepatitis C virus does not integrate into the host genome and thus does not cause direct insertional mutagenesis. HCV-associated HCC develops almost exclusively in the setting of cirrhosis, where decades of necro-inflammatory injury and regenerative hepatocyte proliferation create a permissive environment for accumulation of oncogenic mutations (TP53, CTNNB1/beta-catenin, TERT promoter). Oxidative stress from inflammation also causes DNA damage. This is why HCC risk with HCV is closely tied to cirrhosis severity, and why eradicating HCV with direct-acting antivirals substantially reduces but does not eliminate HCC risk in established cirrhosis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.