Liver Cancer Hepatocellular carcinoma

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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
• Hepatocellular carcinomas (HCCs) are malignant
  tumors of liver parenchymal cells

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• 1.3 of estimated incident cancer cases are in
  the liver and intrahepatic bile duct
• Incidence rates are higher for males than females
  (2-41)
• Higher incidence for African Americans and Asians
  than whites
• 5 year survival rate is approximately 6.9

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• 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 worlds cases occur in China

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• 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

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

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• 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

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• 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 51 to 651
• 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

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• 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

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• 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

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

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• 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

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

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• 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

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• Aflatoxins
• Thorotrast (X-ray contrast material)
• Vinyl Chloride
• Steroid Hormones

• Schistosomiasis
• Liver flukes
• Iron
• Tobacco
• Diet

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

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• 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)

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

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

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• 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

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