Test Catalog

Test ID: L3AFP    
Alpha-Fetoprotein (AFP) L3% and Total, Hepatocellular Carcinoma Tumor Marker, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Distinguishing between hepatocellular carcinoma and chronic liver disease


Monitoring individuals with hepatic cirrhosis from any etiology for progression to hepatocellular carcinoma


Surveillance for development of hepatocellular carcinoma in individuals with a positive family history of hepatic cancer


Surveillance for development of hepatocellular carcinoma in individuals within specific ethnic and gender groups who do not have hepatic cirrhosis, but have a confirmed diagnosis of chronic infection by hepatitis B acquired early in life including:

-African males above the age of 20

-Asian males above the age of 40

-Asian females above the age of 50

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Worldwide, hepatocellular carcinoma is the third leading cause of death from cancer.(1) While hepatocellular carcinoma can be treated effectively in its early stages, most patients are not diagnosed until they are symptomatic and at higher grades and stages, which are less responsive to therapies. Alpha-fetoprotein (AFP) is the standard serum tumor marker utilized in the evaluation of suspected hepatocellular carcinoma. However, increased serum concentrations of AFP might be found in chronic hepatitis and liver cirrhosis as well as in other tumor types (eg, germ cell tumors),(2) decreasing the specificity of AFP testing for hepatocellular carcinoma. Furthermore, AFP is not expressed at high levels in all hepatocellular carcinoma patients, resulting in decreased sensitivity, especially in potentially curable small tumors.


AFP is differentially glycosylated in several hepatic diseases. For example, uridine diphosphate (UDP)-alpha-(1->6)-fucosyltransferase is differentially expressed in hepatocytes following malignant transformation.(3) This enzyme incorporates fucose residues on the carbohydrate chains of AFP. Different glycosylated forms of AFP can be recognized following electrophoresis by reaction with different carbohydrate-binding plant lectins. The fucosylated form of serum AFP, which is most closely associated with hepatocellular carcinoma, is recognized by a lectin from the common lentil (Lens culinaris). This is designated as AFP-L3 (third electrophoretic form of lentil lectin-reactive AFP). AFP-L3 is most useful in the differential diagnosis of individuals with total serum AFP of 200 ng/mL or below, which may result from a variety of benign pathologies such as chronic liver diseases.


AFP-L3 should be utilized as an adjunct to high-resolution ultrasound for surveillance of individuals at significant risk for developing hepatic lesions.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


<4.7 ng/mL




Interpretation Provides information to assist in interpretation of the test results

Alpha-fetoprotein (AFP)-L3 results of 10% or above are associated with a 7-fold increased risk of developing hepatocellular carcinoma. Patients with AFP-L3 at this level should be monitored more intensely for evidence of hepatocellular carcinoma according to current practice guidelines.


A total serum AFP above 200 ng/mL is highly suggestive of a diagnosis of hepatocellular carcinoma. In patients with liver disease, a total serum AFP at this level is near 100% predictive of hepatocellular carcinoma. With decreasing total AFP levels, there is an increased likelihood that chronic liver disease, rather than hepatocellular carcinoma, is responsible for the AFP elevation.


AFP concentrations over 100,000 ng/mL have been reported in normal newborns, and the values rapidly decline in the first 6 years of life.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Tumor marker tests are not specific for diagnosis of malignancy. Some hepatocellular tumors do not synthesize alpha-fetoprotein (AFP). AFP or AFP-L3 should, therefore, not be relied upon alone. Concomitant clinical assessment or imaging is recommended in hepatocellular carcinoma surveillance of high-risk patients and for hepatocellular carcinoma diagnosis.


Test results for AFP are not interpretable if the patient is pregnant.


Values obtained with different assay methods or kits cannot be used interchangeably. The total AFP test value must be obtained using this method (uTASWako i30 AFP-L3 kit) in order to determine the percent AFP-L3. Mayo Clinic Laboratories other AFP tumor marker test, AFP / Alpha-Fetoprotein (AFP) Tumor Marker, Serum; is not suitable for use with AFP-L3 values.


Heterophilic antibodies may be present in the serum of some individuals, which may falsely lower or increase the apparent concentration of AFP or AFP-L3.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Kawai K, Kojima T, Miyanaga N, et al: Lectin-reactive alpha-fetoprotein as a marker for testicular tumor activity. Int J Urol 2005 Mar;12(3):284-289

2. Noda K, Miyoshi E, Kitada T, et al: The enzymatic basis for the conversion of nonfucosylated to fucosylated alpha-fetoprotein by acyclic retinoid treatment in human hepatoma cells: Activation of alpha 1-6 fucosyltransferase. Tumor Biol 2002 Jul-Aug;23(4):202-211

3. Leerapun A, Suravarapu S, Bida JP, et al: The utility of serum AFP-L3 in the diagnosis of hepatocellular carcinoma: Evaluation in a U.S. referral population. Clin Gastroenterol Hepatol 2007 Mar;5(3):394-402

4. Chaiteerakij R, Addissie BD, Roberts LR: Update on biomarkers of hepatocellular carcinoma. Clin Gastroenterol Hepatol 2015 Feb;13(2):237-245. doi: 10.1016/j.cgh.2013.10.038

5. Johnson P, Pirrie S, Cox T, et al: The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers. Cancer Epidemiol Biomarkers Prev 2014 Jan;23(1):144-153. doi: 10.1158/1055-9965.EPI-13-0870

6. Yang JD, Addissie BD, Mara KC, et al: GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score. Cancer Epidemiol Biomarkers Prev 2019 Mar;28(3):531-538. doi: 10.1158/1055-9965