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

Demographics

• 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 ...