 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  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%

 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

 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

 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%

 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

 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

 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

 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

 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

 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

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

 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

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

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

 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)

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

 Vaccine for HCV  Understand molecular pathogenesis of HCC  New targets for chemoprevention of HCC and therapies for established HCC

 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

 Cancer Epidemiology, 3 rd ed Oxford University Press  Centers for Disease Control  American Cancer Society