From the Guidelines
The primary markers used for hepatocellular carcinoma (HCC) diagnosis include alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and AFP-L3 fraction, with a combination of ultrasound (US) and measurement of these markers being the most widely used and effective methods of detecting HCC worldwide. When considering the diagnosis of hepatocellular carcinoma, it is crucial to understand the role of various markers and imaging techniques. The markers used can be divided into serum markers and imaging findings. Serum markers include:
- Alpha-fetoprotein (AFP): The most widely used serum marker, although its sensitivity is limited, with levels above 400 ng/mL considered highly suspicious for HCC 1.
- Des-gamma-carboxy prothrombin (DCP): Serves as a complementary marker that may be elevated when AFP is normal 1.
- AFP-L3 fraction: A glycosylated variant of AFP, offering improved specificity compared to total AFP 1. Imaging findings are also crucial for diagnosis, with characteristic features on contrast-enhanced CT or MRI including arterial phase hyperenhancement followed by washout in the portal venous or delayed phases, often allowing for non-invasive diagnosis without biopsy 1. It is essential to note that the combination of multiple markers typically provides better diagnostic accuracy than any single marker alone, as HCC is heterogeneous and no single marker offers perfect sensitivity and specificity 1. In clinical practice, a combination of US and measurement of tumor markers (AFP/DCP/AFP-L3) every 6 months is recommended for the high-risk population, which includes individuals with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (causes other than HBV or HCV) 1. The ideal surveillance interval should be evaluated from the perspective of cost-effectiveness by considering the clinical status and available resources, with most guidelines recommending a surveillance interval of 6 months for the high-risk population 1. Overall, the diagnosis of hepatocellular carcinoma requires a comprehensive approach, incorporating both serum markers and imaging findings, to ensure early detection and improved patient outcomes.
From the Research
Hepatocarcinoma Markers
The primary markers used for hepatocarcinoma (liver cancer) diagnosis include:
- Alpha-fetoprotein (AFP) 2, 3, 4, 5, 6
- Des-gamma carboxyprothrombin (DCP) 3, 5
- Lectin-bound alpha-fetoprotein (AFP-L3%) 3
- Osteopontin 2
- GP73 2
Diagnostic Performance
The diagnostic performance of these markers varies:
- AFP has a sensitivity of 66% and a specificity of 81% at a cutoff of 10.9 ng/mL for early stage HCC 3
- DCP has a sensitivity of 74% and a specificity of 86% at a cutoff of 40 mAU/mL for early stage HCC 5
- AFP-L3% has a sensitivity of 65% and a specificity of 70% at a cutoff of 10% for early stage HCC 3
- The combination of AFP and DCP increases the sensitivity to 91% but decreases the specificity to 74% 5
Threshold for Diagnosis
The optimal threshold for AFP in diagnosing HCC is controversial:
- A systematic review and meta-analysis found that an AFP threshold of 400 ng/mL had a higher area under the curve (AUC) of the summary receiver operating characteristic (SROC) and Q index compared to thresholds of 200 ng/mL and 20-100 ng/mL 6
- However, other studies suggest that a lower threshold of 10-20 ng/mL may be more sensitive for early stage HCC 3, 5