From the Guidelines
Elevated alpha-fetoprotein (AFP) levels are associated with paracellular carcinoma, particularly in hepatocellular carcinoma (HCC), and can serve as a valuable tumor marker for diagnosis and monitoring, as supported by the most recent guidelines from 2025 1. The value of AFP in paracellular carcinoma is significant, as it can help guide the management of patients with suspected HCC.
- AFP levels are often elevated in HCC, with values exceeding 400 ng/mL, and correlate with tumor size and disease progression.
- However, AFP elevation is not specific to paracellular carcinoma alone and can also be elevated in other conditions such as germ cell tumors, pregnancy, and certain benign liver diseases.
- The sensitivity of AFP for detecting paracellular carcinoma varies, with approximately 60-70% of HCC cases showing elevated levels, as noted in previous studies 1.
- Not all paracellular carcinomas produce AFP, so normal values do not exclude the diagnosis.
- Serial measurements of AFP are more valuable than single readings, as rising levels may indicate tumor recurrence or progression.
- AFP testing should be combined with imaging studies for more accurate diagnosis and monitoring of paracellular carcinoma, as recommended by the 2021 NCCN clinical practice guidelines 1.
- High serum levels of AFP are associated with biologically aggressive HCC and correlated with histoprognostic factors, including microscopic vascular invasion and poor differentiation, as reported in the 2025 EASL clinical practice guidelines 1.
- Elevated AFP levels are also associated with worse prognosis and predict tumor recurrence following liver resection and transplantation, as well as worse survival after locoregional therapies and systemic therapies.
From the Research
Alpha-Fetoprotein (AFP) in Hepatocellular Carcinoma
- The value of AFP in hepatocellular carcinoma (HCC) is a significant marker for diagnosis and monitoring treatment regimens 2.
- Elevated AFP levels are associated with HCC, and a persistently increased AFP level is a risk factor for HCC progression 3.
- The optimal threshold for AFP in diagnosing HCC is controversial, but a systematic review and meta-analysis suggest that a threshold of 400 ng/mL is better than 200 ng/mL in terms of sensitivity and specificity 4.
- AFP response, defined as an AFP reduction by ≥20% within 3 months, is a promising surrogate endpoint for systemic treatment outcomes in HCC 5.
- Patients with baseline AFP < 20 ng/mL are considered not evaluable for AFP change, and those with AFP progression, defined as an increase in AFP by ≥20% within 3 months, have significantly shorter overall survival (OS) than those who do not and those who are not evaluable 5.
AFP Levels in HCC Patients
- Mean elevated AFP levels in HCC patients were 421 +/- 59 microg/ml (range 157-4019 microg/ml) in males and 163 +/- 32 microg/ml (range 101-2341 microg/ml) in females 2.
- Elevated AFP levels are also found in patients with chronic liver disease, hepatitis C, and hepatitis B viral infections 2.
- AFP is an important biomarker for HCC, and its serum expression levels are increased in many patients with HCC 3.
Clinical Significance of AFP
- AFP is a significant marker for HCC, helpful in assessing problems in management of HCC and monitoring treatment regimens 2.
- AFP is also an indicator of HCC risks, mostly in patients with cirrhosis and HCV/HBV infections 2.
- The relationship between AFP and HCC drug resistance is complex, and AFP may function as an immune suppressor, promoting malignant transformation during HCC development and involved in the process of multidrug resistance (MDR) in patients with liver cancer 3.