Description

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).

Epidemiology

Incidence

• 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)

Prevalence

• 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

Genetics
No known genetic pattern

Risk Factors

For HCC

• 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).