Hepatocellular carcinoma (hepatoma) aetiology: Which hepatitis viruses are established risk factors for primary liver cancer?

Introduction:
Hepatocellular carcinoma (HCC) arises in the setting of chronic liver disease and cirrhosis. Viral hepatitis is a major global driver. The two hepatitis viruses consistently implicated as causal risk factors are HBV and HCV.

Given Data / Assumptions:

• We must identify which hepatitis viruses are established causes of HCC.
• Chronicity and oncogenic mechanisms differ between hepatitis viruses.
• HAV does not cause chronic infection and is not a recognized cause of HCC.

Concept / Approach:
HBV is oncogenic via chronic necroinflammation, integration of HBV DNA into the host genome, and expression of HBx protein that affects cell cycle and apoptosis. HCV promotes HCC primarily via chronic inflammation, fibrosis, cirrhosis, and indirect oncogenic signaling; it is an RNA virus and does not integrate like HBV. Both infections are major HCC risk factors worldwide.

Step-by-Step Solution:
Exclude HAV, which causes acute, self-limited hepatitis without chronic carriage. Recognize HBV as a direct and indirect oncogenic virus. Recognize HCV as an indirect oncogenic virus via chronic hepatitis and cirrhosis. Select the combined option covering HBV and HCV.

Verification / Alternative check:
Epidemiologic data show high HCC incidences in regions endemic for HBV or with significant HCV burden; antiviral control reduces HCC risk, supporting causality.

Why Other Options Are Wrong:

• HBV only / HCV only: Each is incomplete because both are established causes.
• HAV / None of these: HAV is not linked to HCC due to lack of chronicity.

Common Pitfalls:
Assuming all hepatitis viruses behave similarly; chronicity is the key determinant for carcinogenic risk.

Final Answer:
Both HBV and HCV are established causes of HCC.