Hepatocellular Carcinoma – Epidemiology


  • Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the fourth major cause of cancer-related death.1
  • Approximately 42,000 cases of primary liver cancer and intrahepatic bile-duct cancer will be diagnosed in the United States in 2019. The majority of primary liver cancers are HCC.2
  • Almost 32,000 people each year die from liver cancer in the United States (US).2
  • The incidence of HCC has more than tripled in the US since 1980, making it the most rapidly increasing cancer in both men and women.2 This increase is primarily due to the rise in hepatitis C virus (HCV)-induced cirrhosis.
  • The rate of death from liver cancer is increasing faster than the rate of death from any other cancer in the US.3
  • Liver cancer has a high mortality rate, with an overall 5-year survival rate of 18% in the US. The 5-year survival rate of localized disease is 31% and falls to 2% for metastatic HCC.2
  • The high mortality rate of liver cancer is largely the result of late-stage diagnosis. Patients with HCC are often asymptomatic until advanced stages of the disease when there are few effective treatment options available.
  • HCC is the leading cause of death among patients with cirrhosis.4
  • Worldwide, ~75% of HCC cases are attributable to chronic hepatitis B virus (HBV) and/or HCV infection. Approximately 50% of all HCC cases worldwide are associated with HBV infection, and a further 25% are linked to HCV.5,6
  • Incidence of HCC increases with HBV viral load and infection duration,7suggesting that chronic infection leads to an accumulation of oncogenic damage.
  • HCC in individuals with HCV-induced cirrhosis has an incidence rate of 4–7/100 person years.8


Risk factors

  • Chronic viral hepatitis. Long-term infection with either HBV or HCV can lead to cirrhosis of the liver and increase the risk of developing liver cancer. The risk of cancer is higher in individuals who drink heavily, ie, ≥6 alcoholic beverages per day. Although most individuals infected with HBV recover within a few months, a small percentage of adults become chronic carriers, with an increased risk of liver cancer. Infected infants and small children have a higher risk of becoming chronic HBV carriers.9
  • In cirrhosis, liver cells become damaged, and scar tissue develops within the liver. The most common causes of cirrhosis in the United States are alcohol abuse and chronic HBV or HCV infections. Most people who develop HCC have evidence of cirrhosis at diagnosis. Cirrhosis can also develop from non-alcoholic fatty liver disease, primary biliary cirrhosis, or inherited conditions, eg, hereditary hemochromatosis.9
  • Heavy alcohol use. Alcohol abuse is the leading cause of cirrhosis in the United States and is linked to an increased risk of HCC.9
  • Type 2 diabetes.This disease increases the risk of liver cancer, particularly in individuals who are heavy alcohol drinkers, have chronic hepatitis infections, or are overweight.9
  • Aflatoxins. These carcinogens are made by some species of the Aspergillus fungus and contaminate peanuts, wheat, soybeans, ground nuts, corn, and rice stored in warm, moist environments. Long-term exposure is a major risk factor for liver cancer, particularly in people with chronic hepatitis infections. Food in the United States and Europe is regulated and tested for aflatoxins.9
  • Chemical exposure. Long-term exposure to vinyl chloride (used in plastics manufacturing), thorium dioxide (Thorotrast, which was used as a contrast agent in radiology), anabolic steroids, and arsenic in drinking water increases the risk of liver cancer.9
  • Schistosomiasis infection.This infection increases the risk of liver damage and cancer. The parasite is found in parts of Asia, Africa, and South America.9


  1. Bray F, Ferlay J, Soerjomataran I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
  2. American Cancer Society. Cancer Facts & Figures 2019. cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html. Accessed December 20, 2019.
  3. Ryerson AB, Eheman CR, Altekruse SF, et al. Annual report to the nation on the status of cancer, 1975-2012, featuring the increasing incidence of liver cancer. 2016;122:1312-1337.
  4. Cirrhosis of the Liver. Hepatocellular carcinoma and cirrhosis of the liver. cirrhosisoftheliver.us. Accessed December 20, 2019.
  5. Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 2010;7:448-458.
  6. Sanyal AJ, Yoon SK, Lencioni R. The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist. 2010;15(suppl 4):14-22.
  7. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
  8. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(suppl 1):S35-S50.
  9. American Cancer Society (ACS). Liver cancer risk factors. org/cancer/liver-cancer/causes-risks-prevention/risk-factors.html. Accessed December 20, 2019.