From the Guidelines
The primary marker for hepatocellular carcinoma (HCC) is alpha-fetoprotein (AFP), which is elevated in approximately 70% of HCC cases, and a combination of ultrasound and AFP testing every 6 months is recommended for surveillance in high-risk patients. Other important serum markers include des-gamma-carboxy prothrombin (DCP, also known as PIVKA-II), AFP-L3 (a glycosylated variant of AFP), glypican-3, and osteopontin 1. These markers are used in combination to improve diagnostic accuracy since AFP alone has limitations in sensitivity and specificity. Imaging biomarkers are equally important in HCC diagnosis, with contrast-enhanced CT, MRI, and ultrasound being essential tools that can detect characteristic vascular patterns of HCC (arterial phase hyperenhancement followed by washout) 1. Newer molecular markers including circulating tumor cells, cell-free DNA, and various microRNAs are emerging as potential biomarkers but are not yet part of routine clinical practice. The use of these markers is crucial because early detection of HCC significantly improves treatment outcomes and survival rates.
Some key points to consider:
- The sensitivity and specificity of AFP can vary, with a sensitivity ranging from 39% to 65% and a specificity ranging from 76% to 97% 1.
- The combination of AFP and ultrasound can improve detection rates, but also increases costs and false-positive rates 1.
- The ideal surveillance interval should be evaluated from the perspective of cost-effectiveness by considering the clinical status and available resources, with a general recommendation of 6 to 12 months for the high-risk population 1.
- Regional differences in epidemiology may affect the choice of surveillance method, and each country could devise its own method of HCC surveillance depending on local epidemiology 1.
Overall, a combination of serum markers and imaging biomarkers is recommended for the diagnosis and surveillance of HCC, with a focus on early detection and improved treatment outcomes.
From the Research
Markers for Hepatocellular Carcinoma (HCC)
- Alpha-fetoprotein (AFP) is one of the most common diagnostic markers for HCC 2, 3
- AFP related parameters, such as AFP mRNA and AFP glycoforms, have diagnostic potential and can be used as complementary tests 2
- HCCR-1 (human cervical cancer oncogene 1) is another marker that can be used in combination with AFP to improve diagnostic rates for HCC 4
- Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin (DCP) are also used as surveillance markers for HCC 5, 6
- The combination of AFP, AFP-L3, and DCP can increase the sensitivity and specificity of HCC diagnosis 5
Diagnostic Values of HCC Markers
- The sensitivity of AFP in HCC diagnosis is around 55.8% 4
- The sensitivity of HCCR-1 in HCC diagnosis is around 44.2% 4
- The combination of AFP and HCCR-1 can increase the sensitivity to 77.2% 4
- The area under the ROC curve of AFP-L3 and DCP in HCC patients with serum AFP <20 ng/ml were 0.724 and 0.779, respectively 6
Clinical Utility of HCC Markers
- AFP is widely used in clinical practice for the screening and diagnosis of HCC 3
- AFP-L3 and DCP can be used to identify individuals with negative imaging results who would benefit from follow-up evaluation 5
- The sensitive AFP-L3% assay can provide great utility in determining HCC recurrence in patients with low AFP concentrations 6