Malignant neoplasms of the liver that arise from parenchymal cells are called hepatocellular carcinomas (accounting for 85% of liver cancers); those that originate in the ductular cells are called cholangiocarcinomas (15% or less). Rare tumors of the liver include angiosarcoma and lymphoma.
Hepatocellular carcinomas are associated with cirrhosis in 85% of cases. In Africa and most of Asia, hepatitis B virus (HBV) infection is a major etiologic factor, and a family history of hepatocellular carcinoma increases the risk synergistically. In the United States and other Western countries, incidence rates have risen rapidly (over twofold since 1978, with slowing of the rate increase since 2006 except in men ages 55–64), presumably because of the increasing prevalence of cirrhosis caused by chronic hepatitis C virus (HCV) infection and nonalcoholic fatty liver disease (NAFLD); however, incidence rates are projected to increase through 2030. In Western countries, risk factors for hepatocellular carcinoma in patients known to have cirrhosis are male gender, age greater than 55 years (although there has been an increase in the number of younger cases), Hispanic or Asian ethnicity, family history in a first-degree relative, overweight, obesity (especially in early adulthood), alcohol use (especially in combination with obesity), tobacco use, diabetes mellitus, hypothyroidism (in women), a prolonged prothrombin time, a low platelet count, and an elevated serum transferrin saturation. The risk of hepatocellular carcinoma is higher in persons with a viral rather than nonviral cause of cirrhosis and may be increased in persons with autoimmune diseases. Other associations include high levels of HBV replication; HBV genotype C; hepatitis D coinfection; elevated serum ALT levels in persons with chronic hepatitis B (in whom antiviral therapy to suppress HBV replication appears to reduce the risk); HCV genotypes 1b and 3; lack of response to antiviral therapy for HCV infection; hemochromatosis (and possibly the C282Y carrier state); aflatoxin exposure (associated with mutation of the TP53 gene); alpha-1-antiprotease (alpha-1-antitrypsin) deficiency; tyrosinemia; and radiation exposure. In patients with the metabolic syndrome and NAFLD, hepatocellular carcinoma may arise from a hepatocellular adenoma in the absence of cirrhosis. Evidence for an association with long-term use of oral contraceptives is inconclusive. Whereas sulfonylurea and insulin use may increase the risk of hepatocellular carcinoma, consumption of coffee, vegetables, white meat, fish, and n-3 polyunsaturated fatty acids; aspirin use; and statin and metformin use in diabetic patients appear to be protective. Genetic polymorphisms associated with lipid trafficking in hepatocytes have been associated with hepatocellular carcinoma.
The fibrolamellar variant of hepatocellular carcinoma generally occurs in young women and is characterized by a distinctive histologic picture, absence of risk factors, unique genomic profiles, and indolent course. Vinyl chloride exposure is associated with angiosarcoma of the liver. Hepatoblastoma, the most common malignant liver tumor in infants and young children, occurs rarely in adults.