Hepatoma (Hepatocellular Carcinoma)



Hepatoma, also known as hepatocellular carcinoma (HCC), is the most common primary malignant tumor of the liver, arising from hepatic parenchymal cells (hepatocytes); 80% are associated with underlying chronic liver disease, most commonly cirrhosis related to hepatitis B and C (exception: rare fibrolamellar type).



  • Second leading cause of cancer-related death worldwide
  • Fifth most common malignancy worldwide, >700,000 new cases per year worldwide (1)[A]
  • 4 to 5 new cases per 100,000 per year of the U.S. population; 120 new cases per 100,000 per year in Asia and sub-Saharan Africa
  • Among known cirrhotics, 2 to 5 cases per 100 cirrhotics per year
  • Incidence increasing since 1980s in the United States (due to increase in hepatitis C infection)
  • In the United States, estimate is 28,720 new cases of primary liver cancer were diagnosed in 2012 and 20,550 deaths.
  • Male > female (mean 3.7:1 for incidence and 2:1 for deaths)


  • Asians/Pacific Islanders > African Americans > Native American > Hispanics > Caucasians
  • Predominant age: median age 65 years in the West, 4th to 5th decades in Asia and Africa
  • Predominant sex: male > female (3 to 4:1)

Etiology and Pathophysiology

  • Cirrhosis accounts for 80–90% of HCC. Alcoholic cirrhosis is most common in the Western world. Reported risk in patients with alcoholic cirrhosis is 3–10% with micronodular pattern.
  • Hepatitis B virus (HBV) and hepatitis C virus (HCV) are independent and synergistic risk factors for HCC.
    • Associated with >70% of cases worldwide
    • Most important factor in Africa and Asia
  • Chronic alcohol use
  • Obesity, type 2 DM, and nonalcoholic fatty liver disease (NAFLD)
  • Chronic tobacco abuse
  • Betel nut chewing (common in Asia)
  • Mycotoxins (aflatoxins): metabolite of the fungus Aspergillus flavus that contaminates foods
  • Vinyl polymers associated with angiosarcoma and, less commonly, HCC

No known genetic pattern

Risk Factors


  • 80–90% of HCC associated with cirrhosis (2)[B]
    • Cirrhosis can be from any etiology: hepatitis B and C, alcoholism, hemochromatosis, nonalcoholic steatohepatitis (NASH), α1antitrypsin deficiency, biliary cirrhosis, autoimmune hepatitis, Wilson disease, glycogen storage disease.
  • Fungal aflatoxins (contaminants of grain in Africa and Asia): synergistic effect with other causes of liver disease
  • Vinyl chloride
  • Thorium dioxide
  • Anabolic steroids
  • Arsenic
  • NAFLD/NASH (3)[C]
  • For fibrolamellar type: no identified risk factors
  • For angiosarcoma: vinyl chloride

General Prevention

  • The major risk factor for HCC is cirrhosis. Prevention of cirrhosis and tumor surveillance in patients with or at risk for cirrhosis is key.
  • Prevent HBV and HCV infection through safe sexual practices, avoidance of shared IV drug paraphernalia, and HBV vaccination.
  • Treat chronic HBV with lamivudine, adefovir, entecavir, tenofovir, or DAA (direct acting antiviral) therapies for chronic HCV, according to guidelines.
  • Avoid excessive alcohol use.
  • Treatment of obesity, NAFLD, NASH
  • Drink >3 cups of coffee per day (4)[A].
  • Statin use is associated with decreased risk of HCC.
  • High-risk individuals
    • Chronic hepatitis with HBV or HCV
    • Alcoholic cirrhosis
    • Genetic hemochromatosis
    • Exposure to vinyl chloride >10 years (Screen every 6 months.)
    • Primary biliary cirrhosis
    • Morbid obesity
  • Screen high-risk patients by ultrasound (US) and α-fetoprotein (AFP) every 6 months (5)[B].
  • HCC progresses from dysplastic nodules to vascular invasion (after tumor is >2 cm in diameter).

There's more to see -- the rest of this topic is available only to subscribers.