Cancer of the Liver and Bile Ducts

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world and the third most common cause of cancer death worldwide.1 More than 500,000 deaths per year are attributed to HCC, representing 10% of all deaths from cancer. In select areas of Asia and Africa, HCC is the most common cause of death due to cancer. The incidence in Europe and the United States is relatively low but is increasing. In Europe, HCC is now the leading cause of death among patients with cirrhosis.2 In the United States, epidemiologic studies have demonstrated a doubling of HCC incidence over the past two decades.3 This increase, which has been attributed to the increasing prevalence of chronic hepatitis C virus (HCV) infection, is expected to continue over the next two decades, given the lag time between the onset of chronic hepatitis and development of HCC. EtiologyUnique among many other cancers, HCC has well-defined major risk factors. Cirrhosis is the strongest predisposing factor for development of HCC, present in 80% of patients. Chronic viral infection is the most frequent major risk factor for development of HCC. In Asia and Africa, hepatitis B viral (HBV) infection is common, whereas in the West and Japan, hepatitis C virus (HCV) is the main risk factor. The association of HCC and HBV infection is one of the most well recognized etiologic relationships in cancer biology. 4 In epidemiologic studies, the prevalence of HBV carriers correlates with incidence of HCC. Chronic HBV carriers have a 100-fold relative risk of developing HCC compared with noncarriers. 5Up to 40% of HBV carriers who develop HCC do not have evidence of cirrhosis, demonstrating the direct carcinogenic potential of HBV infection.6 Prevention of HBV infection reduces the incidence of HCC, as demonstrated in Taiwan, where vaccination of infants reduced the incidence of HBV carriers and simultaneously decreased the incidence of HCC by 60% compared with nonimmunized children. 7,8 In developed countries, HCC arises in cirrhotic livers as a result of HCV infection or excessive alcohol intake. Approximately 170 million people are infected with HCV.9 Vaccination for prevention of HCV infection is currently not available. Prevention is focused on preventing transmission by transfusion of blood products and in halting the progression of infected individuals to cirrhosis by antiviral regimens such as pegylated interferon and ribavirin. Cirrhosis independent of the etiology is thought in most instances to increase the risk of HCC. The degree of association between cirrhosis and HCC, however, is dependent on the primary condition. Cirrhosis from HCV, HBV, alcohol abuse, and hemochromatosis portends a greater risk for HCC than other conditions such as autoimmune hepatitis, primary biliary cirrhosis, a 1 -antitrypsin deficiency, and Wilson's disease, where HCC is uncommon.10