What are the tumor markers for hepatocellular carcinoma (HCC), also known as liver cancer?

From the Guidelines

Ultrasonography (US) is the most appropriate test for liver cancer surveillance, and it should be performed every 6 months in high-risk patients, with or without alpha-fetoprotein (AFP) testing, as the combination of US and AFP does not significantly improve detection rates and may increase false positives and costs. The use of AFP as a serological test for surveillance has suboptimal performance, with a sensitivity of only 63% for early-stage HCC, and its levels can be influenced by various factors, such as flares of HBV or HCV infection, exacerbation of underlying liver disease, or HCC development 1. Other serum markers, such as des-gamma-carboxy prothrombin (DCP) and AFP-L3, have also been evaluated, but their diagnostic performance has often been assessed at an HCC prevalence higher than that expected in the context of surveillance, and their use is not widely recommended for surveillance 1.

Some guidelines, such as the Japanese guidelines, recommend the use of US surveillance every 6 months in high-risk patients, with simultaneous measurements of AFP, DCP, and AFP-L3 fraction, and dynamic computed tomography (CT) or dynamic magnetic resonance imaging (MRI) can be combined with US surveillance in extremely high-risk patients or in patients whose livers are difficult to scan using US 1. However, the most recent and highest-quality study suggests that US alone is sufficient for surveillance, and the addition of AFP or other markers does not significantly improve detection rates and may increase costs 1.

Key points to consider when using liver cancer markers include:

• Ultrasonography (US) is the preferred surveillance modality for high-risk patients
• Alpha-fetoprotein (AFP) has limitations in sensitivity and specificity, and its use as a serological test for surveillance is not widely recommended
• Other serum markers, such as DCP and AFP-L3, have been evaluated, but their use is not widely recommended for surveillance
• Dynamic CT or MRI can be combined with US surveillance in extremely high-risk patients or in patients whose livers are difficult to scan using US
• The most recent and highest-quality study suggests that US alone is sufficient for surveillance, and the addition of AFP or other markers does not significantly improve detection rates and may increase costs 1.

In terms of morbidity, mortality, and quality of life, the use of US surveillance every 6 months in high-risk patients can help detect liver cancer at an early stage, when it is more treatable, and improve patient outcomes 1. However, the use of AFP or other markers as a serological test for surveillance may not significantly improve detection rates and may increase false positives and costs, which can negatively impact patient outcomes 1. Therefore, the use of US surveillance every 6 months in high-risk patients, with or without AFP testing, is the most appropriate approach for liver cancer surveillance, as it can help detect liver cancer at an early stage and improve patient outcomes, while minimizing the risks and costs associated with false positives and unnecessary testing.

From the Research

Liver Cancer Markers

• The following biomarkers are used to detect hepatocellular carcinoma (HCC):
  • Alpha-fetoprotein (AFP)
  • Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3)
  • Des-gamma-carboxy prothrombin (DCP) 2, 3, 4, 5
• These biomarkers can be used alone or in combination to improve the detection of HCC 2, 3, 5
• The combination of AFP and DCP has been shown to have a higher diagnostic value than using either biomarker alone 3
• AFP-L3 and DCP have higher correlation values with the absence of HCC, as well as higher specificity and negative predictive value, than total AFP 2

Biomarker Thresholds

• The established thresholds for these biomarkers are:
  • AFP > 20 ng/mL
  • AFP-L3 > 10% or > 15%
  • DCP > 7.5 ng/mL 2, 5
• Patients with elevated levels of these biomarkers are at increased risk of developing HCC 4, 5

Clinical Applications

• These biomarkers can be used for surveillance, diagnosis, and prognosis of HCC 2, 3, 4, 5
• Biomarker profiling can establish baseline prognosis and identify optimal candidates for liver transplant 5
• The combination of AFP, AFP-L3, and DCP can enhance the diagnostic value of AFP for differentiating between HCC and other liver diseases 3