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Key Clinical Updates in Hepatocellular Carcinoma

The combination of atezolizumab, an immune checkpoint inhibitor, and bevacizumab, an antibody to the VEGF receptor, has been shown to be superior to sorafenib and is now standard first-line therapy.

The combination of nivolumab and ipilimumab has been recommended as second-line therapy after failure of sorafenib.


  • Usually a complication of cirrhosis.

  • Characteristic CT and MRI features may obviate the need for a confirmatory biopsy.


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.

Worldwide, hepatocellular carcinomas are the fourth most common cause of cancer-related deaths and the sixth most common in incidence. They are associated with cirrhosis in 85% of cases. In Africa and most of Asia, hepatitis B virus (HBV) infection (including “occult” HBV infection; see Chapter 16) 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 rose over twofold after 1978, with slowing of the rate increase after 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). Rates appear to have plateaued since 2010 because of improved treatment of viral hepatitis. 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 rarely arise from nonalcoholic steatohepatitis in the absence of cirrhosis. Hepatocellular adenoma may be a precursor for hepatocellular carcinoma (see Chapter 16). 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, ...

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