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 worlds 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 worlds 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 Prospective studies of chronic HBV carriers have shown very high relative risks for HCC Prevention of HBV reduces risk of subsequent HCC
400 and 500 /100,000 compared with 5/100,000 OR ranged from 5:1 to 65:1

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 worlds 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

The Barcelona Clinic Liver Cancer (BCLC) Staging Classification for Hepatocellular Carcinoma
Performance Tumor volume,number Expected and invasiveness BCLC stage status Child-Pugh survival

A Very Early/Early 0

Single < 5 cm or 3 nodes A & B < 3 cm each Large/multinodular A&B

50-75% at 5 yr

B Intermediate

16 months

C Advanced

1-2

Vascular invasion and/or A&B extrahepatic spread Any of the above C

6 months

D End-stage

3-4

< 3 months

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