What is the value of Alpha-Fetoprotein (AFP) in hepatocellular carcinoma?

From the Guidelines

Alpha-fetoprotein (AFP) is a valuable biomarker in hepatocellular carcinoma (HCC) primarily used for diagnosis, monitoring treatment response, and surveillance, with levels above 400 ng/mL considered highly suspicious for HCC in at-risk patients. The use of AFP in HCC diagnosis and management is supported by recent guidelines, including the EASL clinical practice guidelines on the management of hepatocellular carcinoma 1. According to these guidelines, high serum levels of AFP are associated with biologically aggressive HCC and correlated with histoprognostic factors, including microscopic vascular invasion and poor differentiation.

Key Points

• Normal AFP levels are typically below 10 ng/mL, with levels above 400 ng/mL considered highly suspicious for HCC in at-risk patients 1.
• AFP has limitations, as approximately 30-40% of HCC cases do not produce elevated AFP levels (AFP-negative tumors) 1.
• The sensitivity of AFP ranges from 39-65% and specificity from 76-94%, depending on the cutoff value used 1.
• AFP is most useful when combined with imaging studies like ultrasound, CT, or MRI for diagnosis 1.
• Serial measurements of AFP are helpful in monitoring treatment response, with declining levels suggesting effective therapy and rising levels potentially indicating recurrence or progression 1.

Clinical Utility

The clinical utility of AFP is optimized when interpreted in the context of clinical findings, risk factors, and imaging results rather than used as a standalone test 1. Elevated AFP levels can occur in other conditions, including chronic hepatitis, cirrhosis, and pregnancy, which may lead to false positives 1. Therefore, AFP should be used in conjunction with other diagnostic tools and clinical findings to guide the management of patients with suspected HCC.

From the FDA Drug Label

The study enrolled adults with Child-Pugh A and Barcelona Clinic Liver Cancer Stage Category B or C hepatocellular carcinoma, with documented disease progression following sorafenib... Randomization was stratified by geographical region (Asia vs rest of world), ECOG performance status (0 vs 1), alpha-fetoprotein levels (<400 ng/mL vs ≥400 ng/mL), extrahepatic disease (presence vs absence), and macrovascular invasion (presence vs absence).

The value of AFP (Alpha-fetoprotein) in hepatocellular carcinoma is used as a stratification factor, with levels of <400 ng/mL and ≥400 ng/mL being considered. In the study, 51% of patients had AFP levels ≥400 µg/L.

• Key points:
  • AFP levels are used for stratification
  • Threshold: <400 ng/mL vs ≥400 ng/mL
  • Percentage of patients with high AFP: 51% had AFP levels ≥400 µg/L 2

From the Research

Value of AFP in Hepatocellular Carcinoma

• The value of Alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) is a topic of interest in medical research, with various studies investigating its diagnostic significance and optimal threshold 3, 4, 5.
• A systematic review and meta-analysis found that the optimal threshold of AFP for diagnosing HCC was 400 ng/mL, which showed higher sensitivity and specificity compared to thresholds of 200 ng/mL and 20-100 ng/mL 3.
• Another study found that elevated AFP levels were associated with HCC, with mean levels of 421 +/- 59 microg/mL in males and 163 +/- 32 microg/mL in females 4.
• The combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73), and des-gamma-carboxyprothrombin has been shown to improve its accuracy in detecting HCC 5.
• A longitudinal AFP screening algorithm has been proposed to improve the sensitivity of AFP in HCC surveillance, which incorporates screening history to define patient-specific thresholds for positive screens 6.
• Serum AFP levels have been found to be useful in diagnosing tumor recurrence and predicting prognosis in HCC patients treated by hepatic resection, transarterial chemoembolization, and radiofrequency ablation 7.

Diagnostic Significance of AFP

• AFP is recognized as an important blood component with specific diagnostic utilities, and its elevation is associated with various malignant and chronic conditions, including HCC and chronic liver disease 4.
• The diagnostic significance of AFP in HCC has been evaluated in several studies, which have shown that AFP is a significant marker for HCC, helpful in assessing problems in management and monitoring treatment regimens 4, 5.
• However, the utility of AFP is limited by its low sensitivity and specificity, and discrepancies among different methods of measurement 5.

Optimal Threshold of AFP

• The optimal threshold of AFP for diagnosing HCC is a topic of debate, with various studies proposing different thresholds 3, 4, 5.
• A threshold of 400 ng/mL has been proposed as the optimal threshold, which showed higher sensitivity and specificity compared to other thresholds 3.
• However, the choice of threshold may depend on the specific patient population and the clinical context in which AFP is being used 5.