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Primary liver cancer is the fifth most common cancer in the world and the third most common cause of cancer mortality

Primary liver cancer is the fifth most common cancer in the world and the third most common cause of cancer mortality Hepatocellular carcinomas (HCCs) are malignant tumors of liver parenchymal cells. 1.3% of estimated incident cancer cases are in the liver and intrahepatic bile duct

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Primary liver cancer is the fifth most common cancer in the world and the third most common cause of cancer mortality

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  1. Primary liver cancer is the fifth most common cancer in the world and the third most common cause of cancer mortality • Hepatocellular carcinomas (HCCs) are malignant tumors of liver parenchymal cells

  2. 1.3% of estimated incident cancer cases are in the liver and intrahepatic bile duct • Incidence rates are higher for males than females (2-4:1) • Higher incidence for African Americans and Asians than whites • 5 year survival rate is approximately 6.9%

  3. One of the most common malignancies in eastern Asia and sub-Saharan Africa • Incidence up to 90.0/100,000 in some parts of the world • More than 600,000 deaths in 2002 • 44% of the world’s cases occur in China

  4. Incidence increases with age then plateaus when the peak is reached, around 55 to 65 in the United States • Ethnic and familial clustering have been reported • Possible interaction between Hepatitis infection and a major gene

  5. Implicated as the probable cause of HCC in at least 80% of cases worldwide • About 5% of the world’s population(350 million people) is chronically infected with HBV • Lifetime risk of HCC for these individuals is estimated at 10-25%

  6. In low prevalence areas (such as the U.S.), is spread mainly by exposure to contaminated blood through IV drug use or sexual contact with an HBV carrier • In highly endemic areas of Asia, about half of chronic infections result from perinatal transmission • Can also be transmitted through household contacts, contaminated blood or blood products, organ transplantation, or needle-stick

  7. Areas of the world with high mortality rates for HCC also have high HBV infection rates • Cirrhosis is closely related with chronic HBV infection, at least 80% of liver cancers occur in cirrhotic livers • Case control studies in all regions of the world have shown that chronic HBV infection is much more common in HCC cases than controls • OR ranged from 5:1 to 65:1 • Prospective studies of chronic HBV carriers have shown very high relative risks for HCC • 400 and 500 /100,000 compared with 5/100,000 • Prevention of HBV reduces risk of subsequent HCC

  8. Viral DNA is integrated into host cell genome • HBV sequences are present in HCCs • One gene may have important promotional role in hepatocarcinogenesis, but the mechanism is not yet known

  9. Vaccination • 90% preventable with proper use of hepatitis B vaccine • Universal immunization of newborns in Taiwan is associated with at least a 50% reduction in incidence of HCC among adolescents • Part of WHO universal childhood vaccination • Cost reduced from $100 to $1 per pediatric dose

  10. Major viral cause of liver cancer in areas with low HBV prevalence • About 3% of the world’s population (170 million people) is chronically infected with HCV • 3-4 million new infections each year • 2-4% with chronic HCV develop HCC

  11. Transmitted by parenteral route • Intravenous drug use • Hemodialysis • Blood transfusion • Exposure to blood of infected patient • Other routes probably exist but have not been identified

  12. Many epidemiological studies have indicated association • Detection of HCV RNA in tumor and nontumor cirrhotic liver tissue of patients with HCC

  13. Alcohol is a significant risk factor for liver cancer in areas with low HBV and HCV incidence • Evidence indicates that alcohol causes cirrhosis which in turn increases risk of HCC • In high incidence areas, alcohol may exacerbate viral liver damage and promote tumor development

  14. Aflatoxins • Thorotrast (X-ray contrast material) • Vinyl Chloride • Steroid Hormones • Schistosomiasis • Liver flukes • Iron • Tobacco • Diet

  15. Cirrhosis • Immune Function • Genetic Susceptibility • Hemochromatosis • Other Inherited Metabolic Disease • Diabetes Mellitus • Non-alcoholic Steatohepatitis • Primary Sclerosing Cholangitis

  16. Limit exposure of the general populations and workers in certain industries to hepatocarcinogens • Reduce transmission of hepatitis by IV drug use through counseling about risks • Prevent HBV infection (vaccination)

  17. Serum alpha-fetoprotein (AFP) • Limitations: • Senstitivity and specificity • Ultrasonography of the liver • Limitations • Quality of equipment • Skill of operator in identifying small tumors • Cost

  18. Vaccine for HCV • Understand molecular pathogenesis of HCC • New targets for chemoprevention of HCC and therapies for established HCC

  19. 80-95% of HCCs are associated with chronic infection with Hepatitis B or C • HBV infection is preventable by immunization and HCV is preventable through public health measures • If opportunities for intervention are acted upon, HCC could become a minor cause for cancer mortality in the future

  20. Cancer Epidemiology, 3rd ed. 2006. Oxford University Press • Centers for Disease Control • American Cancer Society

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