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For further information, see CMDT Part 39-06: Hepatocellular Carcinoma

Key Features

Essentials of Diagnosis

  • Usually a complication of cirrhosis

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

General Considerations

  • Hepatocellular carcinoma: malignant neoplasm of the liver that arises from parenchymal cells (accounting for 85% of liver cancers)

  • Contrast cholangiocarcinoma: malignant neoplasm that originates in the ductular cells (≤ 15% of liver cancers)

  • Rare tumors of the liver include angiosarcoma and lymphoma

  • Hepatocellular carcinoma risk factors

    • Cirrhosis in general, including nonalcoholic fatty liver disease, and hepatitis B or C in particular

    • Hepatitis B in Africa and Asia

    • Hepatitis C and alcoholic cirrhosis in the West and Japan

    • High levels of HBV replication, HBV genotype C, hepatitis D coinfection

    • Elevated serum ALT levels in persons with chronic hepatitis B (antiviral therapy to suppress HBV replication appears to reduce the risk)

    • HCV infection with lack of response to antiviral therapy

    • HCV genotype 1b

    • Hemochromatosis, aflatoxin exposure (associated with mutation of the TP53 gene), α1-antiprotease (α1-antitrypsin) deficiency, tyrosinemia, and radiation exposure

  • In patients with cirrhosis, additional risk factors include

    • Male sex

    • Age > 55 years

    • Hispanic or Asian ethnicity

    • Family history in a first-degree relative

    • Tobacco use

    • Diabetes mellitus, hypothyroidism, overweight

    • Alcohol use (especially in combination with obesity)

    • HCV infection

    • HBsAg and anti-HBc positivity

    • Elevated serum transferrin saturation

    • Prolonged prothrombin time

    • Low platelet count

  • Fibrolamellar variant of hepatocellular carcinoma

    • Occurs in young women

    • Characterized by a distinctive histologic picture, absence of risk factors, unique genomic profiles, and indolent course

  • Staging in the TNM classification

    • T0: there is no evidence of primary tumor

    • T1a: solitary tumor ≤ to 2 cm

    • T1b: solitary tumor > 2 cm without vascular invasion

    • T2: solitary tumor > 2 cm with vascular invasion or multiple tumors none > 5 cm

    • T3: multiple tumors with at least one > 5 cm

    • T4: single or multiple tumors of any size involving a major branch of the portal or hepatic vein or with direct invasion of adjacent organs other than the gallbladder or with perforation of the visceral peritoneum

    • N1, regional lymph node metastasis

    • M1, distant metastasis

    • F0, no to moderate hepatic fibrosis

    • F1, severe hepatic fibrosis to cirrhosis

  • The BCLC (Barcelona Clinic Liver Cancer) staging system is preferred

    • Includes the Child-Pugh stage, tumor stage, and liver function

    • Has the advantage of linking overall stage with preferred treatment modalities and with an estimation of life expectancy


  • In Africa and most of Asia, hepatitis B virus (HBV) infection is a major etiologic factor

  • In the United States and other Western countries, because of the increasing prevalence of cirrhosis caused by chronic hepatitis C virus (HCV) infection and nonalcoholic fatty liver disease, 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 ...

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