Hepatocellular Carcinoma

Definition

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, often arising in the context of chronic liver disease and cirrhosis.

Epidemiology

• Sixth most common cancer worldwide and third leading cause of cancer-related death
• Higher prevalence in East Asia, sub-Saharan Africa, and regions with high hepatitis B and C prevalence
• Peak incidence: 50–70 years
• Male predominance (2–4:1 ratio)
• Majority of cases occur in patients with underlying chronic liver disease

Etiology

• Chronic hepatitis B virus (HBV) infection (major risk factor globally)
• Chronic hepatitis C virus (HCV) infection
• Alcohol-related liver disease and cirrhosis
• Nonalcoholic fatty liver disease (NAFLD/NASH)
• Aflatoxin exposure, hemochromatosis, primary biliary cholangitis
• Genetic syndromes and metabolic disorders (e.g., Wilson disease)

Pathophysiology

• Chronic liver injury and inflammation lead to fibrosis and cirrhosis
• Hepatocyte regeneration under oxidative stress predisposes to genetic mutations
• Activation of oncogenes (e.g., TERT, CTNNB1) and inactivation of tumor suppressor genes (TP53, AXIN1)
• Angiogenesis and vascular invasion promote tumor growth and metastasis
• Progression can be nodular, massive, or infiltrative