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In 2018, primary liver tumors will be diagnosed in approximately 42,220 new patients in the United States, and approximately 30,200 individuals will die from this disease.1 Worldwide, primary liver tumors remain the second leading cause of death from cancer in males and the sixth leading cause of death from cancer in females.2 Malignant lesions can arise from any of the various cell types that comprise the organ, which include hepatocytes, endothelial cells, and the cells of the intrahepatic bile ducts. The 2 most common hepatic neoplasms are hepatocellular carcinoma (HCC), which accounts for more than 75% of primary liver tumors, and intrahepatic cholangiocarcinoma (ICC), which accounts for 10% to 15%. The remaining primary hepatic neoplasms are hepatic angiosarcoma, epithelioid hemangioendothelioma, and hepatic lymphoma. The focus of this chapter will be on HCC and ICC.

In patients with primary hepatic malignancies, the malignancy itself and any underlying liver disease must be considered as 2 separate but interconnected pathologic processes. The extent of abnormalities associated with each pathologic process directly affects the clinical impact and treatment options.



The incidence of HCC is greatest in areas where exposure to factors that cause chronic HCC injury is heaviest. The incidence of HCC is greatest in sub-Saharan Africa and East Asia, where the incidence is more than 20 cases per 100,000 individuals per year.2 In the United States, the overall incidence of HCC is 6 cases per 100,000 individuals per year; the incidence is highest among Asian, African American, and Hispanic individuals.3 Globally, males have up to 5.7 times the HCC incidence observed in females.2

Risk Factors

There are several risk factors for development of HCC, many of them related to the development of chronic hepatocellular injury (Table 58-1). Some risk factors are independent, while others have potentiating effects. The risk factors most commonly observed in individuals with HCC are the hepatitis viruses: worldwide, 75% to 80% of primary liver tumors are associated with persistent liver infections, particularly hepatitis B (seen in 50%-55% of patients with HCC) or hepatitis C (25%-30%).4 The degree of liver change that results from hepatitis before development of HCC differs between hepatitis B and C. Among patients with hepatitis B, 20% of HCC cases develop before cirrhosis develops, whereas among patients with hepatitis C, HCC almost always arises in the background of significant cirrhosis and fibrosis. The mechanism proposed to explain this difference is that hepatitis B virus directly modulates oncogenes, whereas hepatitis C virus–induced HCC is related to the degree of inflammation.5


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