The burden of cancer is increasing worldwide. Lung, breast, and colorectal cancers are the most commonly diagnosed while lung and liver cancers are the most common causes of cancer death. Liver cancer is the sixth most common cancer worldwide, the second leading cause of cancer-related deaths and one of the few neoplasms whose incidence and mortality rates have been steadily increasing. Liver cancer comprises a heterogeneous group of malignant tumors with different histologic features and unfavorable prognosis that range from hepatocellular carcinoma (HCC; 85–90% cases), intrahepatic cholangiocarcinoma (iCCA; 10%), and other malignancies accounting for <1% of tumors, such as fibrolamellar HCC, mixed HCC-iCCA, epithelioid hemangiothelioma, and the pediatric cancer hepatoblastoma. The burden of liver cancer is increasing globally in almost all countries, and it is estimated to reach one million cases by 2030.
EPIDEMIOLOGY AND RISK FACTORS
Overall, liver cancer accounts for 7% of all cancers (~850,000 new cases each year), and HCC represents 90% of primary liver cancers. The highest incidence rates of HCC occur in Asia and sub-Saharan Africa due to the high prevalence of hepatitis B virus (HBV) infection, with 20–35 cases per 100,000 inhabitants. Southern Europe, and now North America have intermediate incidence rates (10 cases per 100,000), whereas Northern and Western Europe have low incidence rates of less than 5 cases per 100,000 inhabitants. In the United States, liver cancer is ranked number one in terms of increased mortality during the past two decades (Fig. 78-1), with an incidence of 35,000 cases per year. HCC has a strong male preponderance with a male to female ratio estimated to be 2.5. The incidence increases with age, reaching a peak at 65–70 years old. In Chinese and in black African populations (where vertical transmission of HBV occurs), the mean age is 40–50 years. By contrast, in Japan mean age in men is now around 75 years.
Mortality trends of patients with different malignancies in the United States between 1990 and 2009. Changes in cancer mortality across tumor types in the United States. Liver and bile duct cancer rank first in terms of increase mortality for both men and women. (Reprinted with permission from JM Llovet et al: Nat Rev Clin Oncol 12:408, 2015.)
The risk factors for HCC are well established (Fig. 78-2). The main risk factor is cirrhosis—and associated chronic liver damage caused by inflammation and fibrosis—of any etiology, which underlies 80% of HCC cases worldwide and results from chronic infection by HBV or hepatitis C virus (HCV) infection, alcohol abuse, metabolic syndrome, and hemochromatosis (associated to HFE1 gene germ-line mutations). Cirrhotic patients represent 1% of the human population and one-third of them will develop HCC during their lifetime. Long-term follow-up studies have established an annual risk of HCC development of 2% in HBV-infected cirrhotic patients and 3–7% in HCV-infected cirrhotic patients. HCC is less common in cirrhosis associated with alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson’s disease, and cholestatic liver disorders. Predictors of liver cancer development among cirrhotic patients have been associated ...