Hepatocellular Carcinoma (Primary Liver Cancer)

What is Hepatocellular Carcinoma?

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third most common cause of cancer deaths worldwide. HCC accounts for more than 90% of primary liver cancers worldwide. HCC is also known as hepatoma, primary liver cell carcinoma, or primary liver cancer. In the past three decades, HCC has increased threefold due in part to the high prevalence of HCV infection in birth cohorts 1945 – 1965, and the increase in obesity-related fatty liver disease.

What causes HCC?

Risk factors for HCC include chronic hepatitis B and hepatitis C, excessive alcohol consumption, metabolic liver disease (particularly nonalcoholic fatty liver disease), and exposure to dietary toxins such as aflatoxins and aristolochic acid. Cirrhosis is when the liver is scarred and undergoes chronic cycles of necrosis and regeneration, resulting in poor function. This is mostly due to long-term exposure to hepatitis or alcohol.

What are the symptoms of HCC?

Symptoms include abdominal pain or tenderness (particularly in the right-upper part of the abdomen), an enlarged abdomen, right shoulder pain, bloating, decreased appetite, nausea, unexplained weight loss, easy bruising/bleeding, and unexplained fevers. Jaundice and swelling of the abdomen/legs can occur in more advanced liver cancer. HCC is asymptomatic in its early stages. Many patients with HCC do not develop symptoms until the advanced stages of the disease.

How is HCC diagnosed?

Tests and procedures used to diagnose HCC include:

  • A physical examination may show an enlarged, tender liver.

  • Imaging tests such as ultrasound (US), computed tomography (CT), or magnetic resonance imaging (MRI) may reveal a mass in the liver.

  • Blood tests of liver enzymes or function may show abnormal variations, or tumor markers such as serum alpha-fetoprotein (AFP) may be elevated.

  • Recent advances in ultrasound equipment have made it possible to provide information on malignancy potential and localization diagnosis of HCC. 

  • A liver biopsy may reveal cancer after a tissue sample is removed during surgery and examined under a microscope by a pathologist.

What are the stages of HCC?

While there are multiple staging systems for HCC, the one most commonly used is the Barcelona Clinic Liver Cancer (BCLC) staging and treatment system outlined here. BCLC classifies patients based on tumor burden which considers the number of lesions, tumor size, vascular invasion or metastasis, and degree of liver dysfunction. Studies show that the BCLC staging system has the best predictive power for estimating survival in the U.S. 

Very Early Stage (0)

Single tumor less than 2 cm with preserved liver function

Early Stage (A)

Single tumor, or less than 3 nodules each less than 3 cm with preserved liver function.

Intermediate Stage (B)

Multiple tumors that do not invade blood vessels or extend outside of the liver with preserved liver function.

Advanced Stage (C)

A tumor(s) that invade the blood vessels or a nearby organ (other than the gallbladder) with or without preserved liver function.

Terminal Stage (D)

Cancer has spread to other parts of the body (e.g., lungs, bones). Tumors can be any size or number, and nearby lymph nodes may or may not be involved. Liver function is compromised. End-stage liver function.

Liver Cancer Staging System

Sources: Experimental & Molecular Medicine, Mayo Foundation for Medical Education and Research, and National Institutes of Health © March 2022