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Hepatocellular carcinoma (HCC) is the most common primary liver cancer accounting for 90% of all liver malignancies and has become the fastest-rising cause of cancer-related deaths in the United States. Worldwide, HCC is the sixth most common cancer and the third most common cause of cancer-related deaths (1). In the United States, 28,720 new cancers of the liver and intrahepatic bile duct are expected in 2012, with an estimated 20,550 deaths (2). In the United States, the incidence of HCC has tripled while the 5-year survival rate has remained below 12% during the past two decades (3). Treatment outcomes are dependent on the clinical stage at diagnosis. While patients with early stage HCC can be cured by surgical resection or liver transplantation, advanced HCC carries a poor prognosis with a median survival of less than 1 year.


HCC is a heterogeneous disease in terms of etiology and underlying risk factors (Table 46-1) with significant geographic variation in distribution worldwide (3). It occurs most frequently in Southeast Asia and sub-Saharan Africa. The prevalence of HCC in these areas is more than 100/100,000 population, whereas in Europe and North America it is estimated as 2–4 per 100,000 population.


HCC develops commonly, but not exclusively, in a setting of liver cell injury, which leads to inflammation, hepatocyte regeneration, liver matrix remodeling, fibrosis, and ultimately cirrhosis. The major etiologies of liver cirrhosis are diverse and include chronic hepatitis B (HBV) and C (HCV), alcohol consumption, certain medications or toxic exposures, and genetic metabolic diseases. More than 80% of HCC occurs in HBV-infected populations worldwide. The geographic distribution of HCC correlates with the prevalence of HBV. HCC incidence is greatest in Eastern Asia and sub-Saharan Africa, which correlates with the highest rates of chronic HBV infection in these areas. It is estimated that the incidence of cirrhosis is approximately 25–50% in HBV infection and HBV infection may increase the risk of HCC development up to 100-fold.

HCV infection has been increasingly recognized as another serious risk factor for HCC, particularly in Western Europe and the United States. It is estimated that approximately 3.9 million people in the United States and 100 million people worldwide are infected with HCV. Approximately 70–80% HCV-infected patients will develop chronic HCV infection and 15–20% will eventually develop cirrhosis. Once cirrhosis develops, HCC will develop at a rate of 1–4% per year with 5–10% of all patients with chronic HCV infection developing HCC eventually.

Among other risks, alcohol-induced cirrhosis is an established risk for ...

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