Test Catalog

Test Id : HCCGS

Hepatocellular Carcinoma Risk Panel with GALAD Score, Serum

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

Risk assessment for development of hepatocellular carcinoma in patients with chronic liver disease

Highlights

This test includes a GALAD (gender, age, alpha-fetoprotein [AFP]-L3, AFP, des-gamma-carboxy prothrombin [DCP]) model score calculation to calculate the probability of hepatocellular carcinoma (HCC). The GALAD model has been demonstrated to have higher diagnostic accuracy for the detection of HCC when compared to the use AFP, AFP-L3, and DCP markers alone or in combination. The performance of the GALAD score has also been reported to be superior to ultrasound for HCC detection.

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
L3AFP AFP-L3% and Total AFP, S Yes Yes
DCP Des-Gamma-Carboxy Prothrombin, S Yes Yes
GAL1 GALAD Model Score No Yes
GAL2 Probability of HCC No Yes

Method Name
A short description of the method used to perform the test

Isotachophoresis with Laser-Induced Fluorescence

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

HCC Risk Panel with GALAD Score, S

Specimen Type
Describes the specimen type validated for testing

Serum

Ordering Guidance

GALAD score testing (this test) should not be performed for pregnant patients as alpha-fetoprotein results are elevated during pregnancy.

Necessary Information

Gender and age are required.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 0.5 mL

Collection Instructions: Centrifuge and aliquot serum.

Forms

If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Gastroenterology and Hepatology Client Test Request (T728)

-Oncology Test Request (T729)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.25 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 90 days
Refrigerated 5 days

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

Risk assessment for development of hepatocellular carcinoma in patients with chronic liver disease

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

Worldwide, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death.(1) While HCC 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 HCC. 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 HCC. Furthermore, AFP is not expressed at high levels in all HCC patients, resulting in decreased sensitivity, especially in potentially curable small tumors.

 

AFP-L3:

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 HCC 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 less, which may result from a variety of benign pathologies, such as chronic liver diseases.

 

Des-gamma-carboxy prothrombin (DCP):

(DCP, also known as the protein induced by vitamin K absence or antagonist II (PIVKA-II), is an abnormal form of the coagulation protein, prothrombin. DCP is a nonfunctional prothrombin resulting from a lack of carboxylation of 10 glutamic acid residues in the N-terminal portion of the molecule. In normal liver, prothrombin undergoes post-translational carboxylation before release into the peripheral blood. The carboxylation converts specific amino-terminal glutamic acid residues to gamma-carboxyglutamic acid. The vitamin K dependent carboxylase responsible for the carboxylation is absent in many HCC cells, and an abnormal prothrombin with all or some of unconverted glutamic acid is secreted. Therefore, this noncarboxylated form (DCP) has been used as an HCC biomarker.

 

DCP is considered a complementary biomarker to AFP and AFP-L3 for assessing the risk of developing HCC. The elevation of both AFP-L3 and DCP indicate progression of HCC, albeit they reflect different features of the progression. In a prospective study of patients in the United States with an established diagnosis of HCC, the sensitivities for AFP, AFP-L3, and DCP were 68%, 62%, and 73%, respectively. When the 3 markers were combined, the sensitivity was 86%. In another study, DCP levels were shown to correlate with tumor size and metastatic HCC. In this study, compared to AFP and AFP-L3, DCP had the highest sensitivity (87%) and the highest positive predictive value (87%) in patients with HCC due to chronic hepatitis B and C infections. A number of studies have shown that elevated serum DCP is significantly related to portal vein invasion or intrahepatic metastasis, which significantly affect prognosis for patients with HCC.

 

DCP can be elevated in other conditions besides HCC. Conditions such as obstructive jaundice, intrahepatic cholestasis causing chronic decrease in vitamin K, and ingestion of drugs such as warfarin or wide-spectrum antibiotics can result in high concentrations of DCP. In addition, 25% to 50% of patients with HCC will have a DCP value within the reference range. Because of this, a normal DCP value does not rule out HCC.

 

Gender, Age, AFP-L3, AFP, DCP (GALAD) Score and Probability of HCC:

Biomarkers of HCC include AFP, AFP-L3, and DCP. The GALAD model combines these three biomarkers with the patient's gender and age to estimate the probability of HCC in patients with chronic liver disease based on the following equation Z = -10.08 + 0.09 x age + 1.67 x sex + 2.34 log(10) (AFP) + 0.04 x AFP - L3 + 1.33 x log(10) (DCP), where sex = 1 for males, 0 for females. The probability estimate of HCC is calculated as follow Pr(HCC) = exp(Z)/(1 + exp[Z]).

 

The GALAD model has been demonstrated to have higher diagnostic accuracy for the detection of HCC when compared to the use AFP, AFP-L3, and DCP markers alone or in combination. The performance of the GALAD score has also been reported to be superior to ultrasound for HCC detection.

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 ALPHA-FETOPROTEIN (AFP):

<4.7 ng/Ml

 

AFP L3-PERCENT:

<10%

 

DES-GAMMA-CARBOXY PROTHROMBIN:

<7.5 ng/mL

 

GAL1:

Not applicable

 

GAL2:

Not applicable

Interpretation
Provides information to assist in interpretation of the test results

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

 

Total serum AFP results above 200 ng/mL are highly suggestive of a diagnosis of HCC. In patients with liver disease, a total serum AFP level above200 ng/mL is near 100% predictive of HCC. With decreasing total AFP levels, there is an increased likelihood that chronic liver disease, rather than HCC, is responsible for the AFP elevation.

 

Based on a retrospective study at Mayo Clinic, for patients with total AFP levels 200 ng/mL or less, AFP-L3 specificity approaches 100% for HCC when its percentage exceeds 35% of the total AFP.(4)

 

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.

 

Des-gamma-carboxy prothrombin (DCP):

In patients with an elevated DCP result (> or =7.5 ng/mL), the risk of developing HCC is 36.5% (95% CI 23.5%-49.6%). The risk of developing HCC with a negative DCP result (<7.5 ng/mL) is 7.6% (95% CI 4.4%-10.8%).

 

Gender, Age, AFP-L3, AFP, DCP (GALAD) Score and Probability of HCC:

The probability of the presence of HCC is estimated from the GALAD model score. Higher GALAD model scores correlate with increased risk of HCC. The area under the curve (AUC) of a receiver operating characteristic (ROC) curve of the GALAD score was 0.95 for all HCC detection, and 0.92 for the detection of early stage HCC. Additionally, the AUC of the GALAD score (0.95) was higher than that of ultrasound alone for all HCC detection (AUC of 0.82, P <0.01).

 

The sensitivity and specificity performance characteristics of the GALAD score for HCC will be influenced by the selected GALAD score cut-off. For example at an optimal AUC cutoff of -0.76, the GALAD score had 91% sensitivity and 85% specificity for HCC detection. At a more specific GALAD score cutoff of 0.88, the observed sensitivity was 80% for HCC detection with an observed specificity of 97%.

 

The GALAD model was developed and validated in patient cohorts with a prevalence of HCC ranging from 35% to 49%. The performance of the model may be altered in populations with different HCC prevalence. In addition, the clinical performance of the GALAD score varies by etiology of HCC and therefore may be different in different regions of the world.

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

Serum markers are not specific for malignancy, and values may vary by method. Do not interpret alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as absolute evidence of the presence or absence of malignant disease. Results should be used in conjunction with information from the clinical evaluation of the patient, cytology, and imaging procedures.

 

Values obtained with different assay methods or kits cannot be used interchangeably.

 

Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating anti-animal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results in the AFP-L3 and DCP assays.

 

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

 

DCP-producing tumors other than hepatocellular carcinoma can show elevated DCP values. Liver disease caused by other etiologies such as alcohol-induced liver disease, hemochromatosis, Wilson disease, autoimmune hepatitis, and steatohepatitis have not been studied with the DCP assay.

 

Medications containing vitamin K preparations may cause a negative bias with DCP values. Medications containing vitamin K antagonist or antibiotic may cause a positive bias with DCP values.

 

The total AFP and AFP-L3 test values must be obtained using the uTASWako i30 in the GALAD score calculation.

Clinical Reference
Recommendations for 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 J Urol 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. Carr B, Kanke F, Wise M, Satomura S: Clinical evaluation of Lens culinaris agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States. Dig Dis Sci 2007;52:776-782

6. Durazo FA, Blatt LM, Corey WG, et al: Des-gamma-carboxy prothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol 2008;23:1541-1548

7. Marrero JA, Feng Z, Wang Y, et al: Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009;137:110-118

8. Bertino G, Ardiri AM, Calvagno GS, et al: Prognostic and diagnostic value of des-gamma-carboxy prothrombin in liver cancer. Drug News Perspect 2010 Oct;23(8):498-508

9. 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

10. Berhane S, Toyota H, Tada T, et al: Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients. Clin Gastroenterol Hepatic 2016 Jun;14(6):875-886

11. 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

12. 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

Method Description
Describes how the test is performed and provides a method-specific reference

Testing is performed using the uTASWako i30 instrument and the test system reagents.

 

Alpha-Fetoprotein (AFP) L3:

Total AFP is measured by laser-induced fluorescence with separation of the lentil lectin-reactive AFP-L3 and lectin nonreactive forms of AFP by isotachophoresis of their immune-complexes. Results are expressed as the percent ratio of AFP-L3 to total AFP.(Package insert: uTASWako i30 AFP-L3, Wako Diagnostics, Richmond, VA, 06.1.24K02)

 

Des-Gamma-Carboxy Prothrombin (DCP):

Sample is added to the reagent well with the fluorescent dye labeled antihuman prothrombin antibody (mouse monoclonal) to form the primary immunocomplex. The second labeled antibody solution, anion-conjugated antihuman DCP antibody (mouse monoclonal), is concentrated by isotachophoresis when voltage is applied. The concentrated anion-conjugated antibody then reacts with the primary immunocomplex to form the secondary immunocomplex. This secondary complex is further concentrated during isotachophoresis and is separated from unbound fluorescent dye-labeled antibody by capillary gel electrophoresis. The remaining dye labeled DCP is measured by laser-induced fluorescence. The concentration of DCP in the specimen is directly proportional to the amount of fluorescence.(Package insert: uTASWako i30 DCP, Wako Diagnostics, Richmond, VA. V 11.03.08K02)

 

Gender, Age, AFP-L3, AFP, DCP (GALAD) Model Score and Probability of Hepatocellular Carcinoma (HCC):

The GALAD model is a statistical model for estimating the likelihood of HCC in patients with chronic liver disease. The GALAD score is calculated based on gender, age, and measured concentrations of AFL-L3, AFP and DCP.

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday, Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 4 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

12 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82107

83951

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
HCCGS HCC Risk Panel with GALAD Score, S 96452-8
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
TAFP Total AFP, S 1834-1
L3 %L3 42332-7
INT67 Interpretation 69048-7
DCP Des-Gamma-Carboxy Prothrombin, S 34444-0
GAL1 GALAD Model Score 96450-2
GAL2 Probability of HCC 96709-1

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports