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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), alpha-1-antiprotease (alpha-1-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 ≤ 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


  • Worldwide, hepatocellular carcinomas are the fourth most common cause of cancer-related deaths and the sixth most common cancer in incidence

  • 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 have risen rapidly (over twofold since 1978 with some ...

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