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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, 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 that 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 < or =200 ng/mL, 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, as described below.

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.

 

TOTAL %L3AFP

AFP-Total Serum (ng/mL)

AFP-L3/Total

AFP (%)*

 

 

Interpretation

>200

NA

Total AFP concentrations >200 ng/mL are consistent with hepatocellular carcinoma. It is suggested that these results be correlated with imaging studies.

For children <12 months of age: AFP concentrations over 100,000 ng/mL have been reported in normal newborns and the values rapidly decline in the first 6 months of life.

10-200

>35

The %AFP-L3 for this individual is in the range that is predictive of the presence of hepatocellular carcinoma, including very small preclinical hepatocellular carcinoma. In this group of patients, the positive predictive value and specificity of AFP-L3 approaches 100% for hepatocellular carcinoma.

For children <12 months of age: AFP concentrations over 100,000 ng/mL have been reported in normal newborns and the values rapidly decline in the first 6 months of life.

10-200

10-35

The %AFP-L3 for this individual is in the range that is suspicious for developing hepatocellular carcinoma. In this group of patients, there is an increased risk of developing hepatocellular carcinoma. Monitoring by imaging and AFP testing is suggested.

For children <12 months of age: AFP concentrations over 100,000 ng/mL have been reported in normal newborns and the values rapidly decline in the first 6 months of life.

10-200

<10

The %AFP-L3 for this individual is in the range that is not informative regarding hepatocellular carcinoma. These marker levels are associated with chronic liver diseases as well as with a minority of hepatocellular carcinomas, but do not distinguish between these pathologies. Monitoring by imaging and AFP testing is suggested.

For children <12 months of age: AFP concentrations over 100,000 ng/mL have been reported in normal newborns and the values rapidly decline in the first 6 months of life.

<10

<10

The %AFP-L3 for this individual is in the range that is not informative regarding hepatocellular carcinoma. These marker levels are associated with normal liver, chronic liver diseases as well as with a minority of hepatocellular carcinomas, but do not distinguish between these states.

*Percent AFP-L3/total AFP values were determined in a retrospective clinical study (Leerapun A, Suravarapu S, Bida JP, et al: The utility of lens culinaris agglutinin-reactive alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: evaluation in a United States referral population. Clin Gastroenterol Hepatol 2007;5:394-402)

Interpretation Provides information to assist in interpretation of the test results

Total serum alpha-fetoprotein (AFP) >200 ng/mL is highly suggestive of a positive diagnosis of hepatocellular carcinoma. In patients with liver disease, a total serum AFP of >200 ng/mL 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.

 

For patients with total AFP levels < or = 200 ng/mL, the ratio of the AFP-L3 to the total AFP is predictive of the presence of hepatocellular carcinoma, including a very small preclinical hepatocellular carcinoma. In this group of patients, the positive predictive value and specificity of AFP-L3 approaches 100% for hepatocellular carcinoma when its percentage exceeds 35% of the total AFP.(4)

 

The specificity of AFP-L3 decreases to approximately 63% as the percentage of AFP-L3 decreases from 35% to 10%. Either chronic liver disease or hepatocellular carcinoma is possible in these cases and additional clinical findings are necessary to obtain a diagnosis.

 

AFP-L3 > or =10% is associated with a 7-fold increased risk of developing hepatocellular carcinoma. Patients with AFP-L3 > or =10% should be monitored more intensely for evidence  of hepatocellular carcinoma following current practice guidelines.

 

This test provides no diagnostic information when either the total AFP is <10 ng/mL or AFP-L3 is <10%. These results may be seen in either normal subjects or patients with hepatocellular carcinoma or chronic liver diseases.

 

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.

 

The data shown in Reference Values lists the decision making levels established in a retrospective study at the Mayo Clinic (see Supportive Data). Diagnostic cutoffs may differ slightly in other patient populations.

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 a diagnosis of malignancy. Sensitivity of hepatocellular carcinoma detection using alpha-fetoprotein (AFP)-L3 is >70%. However, some hepatocellular tumors do not synthesize 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 (Wako LBA AFP-L3 kit) in order to determine the percent AFP-L3. Mayo Medical Laboratories other AFP tumor marker test, #8162 Alpha-Fetoprotein (AFP) Tumor Marker, Serum; is not suitable for use with AFP-L3 values.

 

This test cannot distinguish between chronic liver disease and hepatocellular carcinoma when AFP-L3 < or =35% and total AFP is between 10 ng/mL and 200 ng/mL.

 

This test cannot distinguish between normal patients and those with chronic liver disease or hepatocellular carcinoma when AFP-L3 is < or =10% and total AFP is <10 ng/mL.

 

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.

Supportive Data

Alpha-fetoprotein (AFP)-L3 reference values are based on a Mayo study of 167 patients with confirmed hepatocellular carcinoma and in 107 patients with benign liver disease. AFP-L3 >35 was 100% specific for hepatocellular carcinoma. (Leerapun A, Suravarapu S, Bida JP, et al: The utility of serum AFP-L3 in the diagnosis of hepatocellular carcinoma: valuation in a U.S. referral population. Clin Gastroenterol Hepatol 2007; In Press)

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Okuda K: Hepatocellular carcinoma. J Hepatol 2000;32(Suppl 1):225-237

2. Kawai K, Kojima T, Miyanaga N, et al: Lectin-reactive alpha-fetoprotein as a marker for testicular tumor activity. Int JUrol 2005;12:284-289

3. 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;23:202-211

4. 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;5(3):394-402

5. Package insert: LBA AFP-L3. Wako Diagnostics, Richmond, VA. 06.1.24K02

6. Wako Pure Chemical Industries, Ltd. Specimen Stability Bulletin, March 22nd, 2006