α-Fetoprotein (AFP) With AFP-L3%

Serum

0.5 mL

0.2 mL (Note: This volume does not allow for repeat testing.)

Red-top tube or gel-barrier tube

The AFP-L3% assay is intended for use in the assessment of risk for the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases.¹

Samples from patients with acute hepatitis or fulminant hepatitis can show high values of AFP-L3% and AFP. Pregnancy can cause high values of AFP-L3% and AFP. AFP producing tumors other than HCC can show high values of AFP-L3% and AFP. Bilirubin at a concentration >20 mg/dL can cause a negative influence on the AFP-L3% and AFP values. Glucose at a concentration >600 mg/dL can cause a negative influence on AFP-L3% values. With regard to AFP, normal values apply only to males and nonpregnant females. Normal infants younger than 18 months of age may have higher values.

Results for this test should not be used as absolute evidence of presence or absence of malignant disease without confirmation of the diagnosis by another medically established diagnostic product or procedure. Values obtained with different assay methods or kits cannot be used interchangeably.

Liquid-phase binding assay

See table.

Serum AFP levels are markedly elevated in the neonate because AFP is synthesized in large quantities during embryonic development by the fetal yolk sac and by the fetal liver.² Serum AFP concentrations decrease gradually after birth until they reach adult levels by 12 to 18 months of age.² Due to fetal production, AFP becomes elevated in maternal serum during pregnancy.² Pathologically, increased AFP levels have been associated with both acute and chronic liver disease as well as hepatocellular carcinoma (HCC).^2,3 AFP can also be elevated in a number of other malignancies including gastric, lung, pancreatic, biliary tract, and testicular carcinomas.² Patients with chronic liver disease are at a greatly increased risk for developing HCC.^2,3 Early detection of HCC is important, especially in high-risk populations.³ Unfortunately, increased AFP is often observed in patients with chronic liver disease that has not progressed to HCC.^2,3 This serves to limit the utility of AFP measurements as an early indicator of progression to HCC in these patients.^2,3

AFP is a glycoprotein with a single glycosylation site at a specific arginine residue.² Three glycosylation variants occur in serum reflecting different carbohydrate chains linked at this single position.² These variants can be differentiated based on their relative binding to a lectin (carbohydrate-binding protein) isolated from lentil seeds.⁴ This lectin, referred to as Lens culinaris agglutinin (LCA), binds to variants AFP-L1, AFP-L2, and AFP-L3 with increasing affinity. AFP-L1, which has the weakest binding to LCA, is the predominant fraction in patients with nonmalignant liver diseases, such as chronic hepatitis and liver cirrhosis.²

A number of clinical studies have shown that the AFP-L3 fraction (the glycosylation variant that binds strongest to LCA) is produced predominantly by malignant cells.^2,5 Liver cancer cells that express AFP-L3 have been shown to have an increased tendency for early vascular invasion and development of intrahepatic metastasis.^3,5 Studies suggest that the measurement of AFP-L3% can allow earlier detection of HCC than imaging techniques.^5-7 Elevated AFP-L3% has been associated with poorer prognosis for patients with HCC.^8-17 In a recent multisite clinical trial, elevated AFP-L3% (≥10%) has been shown to be associated with a sevenfold increase in the risk of developing HCC within the next 21 months.¹ This study concluded that patients with elevated serum AFP-L3% should be more intensely evaluated for evidence of HCC according to the existing HCC practice guidelines in oncology.¹