To help diagnose and monitor therapy for certain cancers of the liver, testicles, or ovaries
When your healthcare practitioner suspects that you have certain cancers of the liver, testicles, or ovaries; at intervals during and after treatment for one of these cancers; sometimes when you have a condition that increases your risk of liver cancer, such as chronic hepatitis or cirrhosis
A blood sample drawn from a vein in your arm
Alpha-fetoprotein (AFP) is a protein produced primarily by the liver in a developing baby (fetus). AFP levels are normally elevated when a baby is born and then decline rapidly. Outside of pregnancy and birth, liver damage and certain cancers can increase AFP levels significantly. This test measures the level of AFP in your blood.
AFP is produced whenever liver cells are regenerating. With chronic liver diseases, such as hepatitis and cirrhosis, AFP may be chronically elevated. Very high concentrations of AFP may be produced by certain tumors. This characteristic makes the AFP test useful as a tumor marker. Increased amounts of AFP are found in many people with the most common type of liver cancer called hepatocellular carcinoma and in a rare type of liver cancer that most commonly occurs in infants called hepatoblastoma. They are also found in some people with cancers of the testicles or ovaries.
AFP exists in several different forms. The standard AFP test is for a total AFP, one that measures all of the AFP forms together. This is the primary AFP test used in the United States.
One of the AFP forms is called L3. The AFP-L3% test is a relatively new test that compares the amount of AFP-L3 to the total amount of AFP. An increase in the percentage of L3 is associated with increased risk of developing hepatocellular carcinoma in the near future and of having a poorer prognosis, as the L3-related cancers tend to be more aggressive.
Among people with low total AFP, AFP-L3 can be higher in those with hepatocellular carcinoma than in people with benign liver diseases. Tumor markers including total AFP and AFP-L3 are used in addition to ultrasound for surveillance of hepatocellular carcinoma in Japan. This practice is different from that in the U.S. and Europe, but the two tests are occasionally ordered by healthcare practitioners in the U.S.
Alpha-fetoprotein (AFP) is used as a tumor marker to help detect and diagnose cancers of the liver, testicles, and ovaries. Though the test is often ordered to monitor people with chronic liver diseases such as cirrhosis, chronic hepatitis B or hepatitis C because they have an increased lifetime risk of developing liver cancer, most current guidelines do not recommend this use. A healthcare practitioner may order an AFP test, along with imaging studies, to try to detect liver cancer when it is in its earliest and most treatable stages.
If you have been diagnosed with hepatocellular carcinoma or another form of AFP-producing cancer, an AFP test may be used to help monitor your response to therapy and to monitor for cancer recurrence.
An AFP-L3% is sometimes also ordered to compare the amount of the AFP form called AFP-L3 to the total amount of AFP. The AFP-L3% test is not yet widely used in the U.S. but has gained wider acceptance in other countries such as Japan. The test is used to help evaluate the risk of developing hepatocellular carcinoma, especially if you have chronic liver disease, and also to evaluate the response of your hepatocellular carcinoma to treatment.
A healthcare practitioner may order an AFP blood test:
An AFP-L3% is sometimes ordered to help evaluate the risk of hepatocellular carcinoma when you have chronic liver disease or to test the effectiveness of treatment of hepatocellular carcinoma or monitor for its recurrence.
Increased AFP levels may indicate the presence of cancer, most commonly liver cancer, cancer of the ovary, or germ cell tumor of the testicles. However, not every liver, ovarian, or testicular cancer will produce significant quantities of AFP.
Elevated levels may sometimes be seen with other cancers such as stomach, colon, lung, breast, and lymphoma, although it is rarely ordered to evaluate these conditions. Other diseases such as cirrhosis and hepatitis can also cause increased levels.
When AFP is used as a monitoring tool, decreasing levels indicate a response to treatment. If AFP levels after cancer treatment do not significantly decrease, usually to normal or near normal levels, then some of the tumor tissue may still be present.
If your AFP levels begin to increase, then it is likely that the cancer is recurring. However, since AFP can be increased in hepatitis or cirrhosis, AFP levels can sometimes be misleading. If your AFP levels are not elevated prior to treatment, then the test will not generally be useful to monitor the effectiveness of your treatment or to monitor for recurrence.
When you have chronic liver disease and your AFP levels go from normal or moderately elevated to greatly elevated, your risk of developing liver cancer increases. When total AFP and AFP-L3% are significantly elevated, then you have an increased risk of having or developing hepatocellular carcinoma in the next year or two. However, both AFP and AFP-L3% concentrations can be elevated, and fluctuate, when you have chronic hepatitis and cirrhosis. In these cases, a sharp increase in AFP is more important than the actual numerical value of the test result.
Not every person with increased AFP and AFP-L3% test results has cancer or will develop liver cancer. The AFP and AFP-L3% tests are not diagnostic per se; they are indicators. They must be used in conjunction with information from your medical history and physical examination as well as histopathological examination and imaging studies to look for the development of tumors.
Although these tests can provide useful information, they are not as specific or sensitive as healthcare practitioners would wish. AFP can temporarily increase whenever the liver is injured and regenerating, and moderate elevations can be seen with a variety of conditions. Because of this, AFP testing cannot be used solely to diagnose cancer. In addition, not every cancer will produce AFP, so you could still have cancer even when the AFP is normal. For these reasons, the AFP test is not used to screen the general population for cancer.
AFP is not only a tumor marker. Because AFP is produced by the fetus, levels are normally higher in pregnant women and in their newborns. For more information on AFP testing during pregnancy, see the Second Trimester Maternal Serum Screen.
This cancer usually occurs when you have chronic scarring of the liver, called cirrhosis. Most commonly, this is caused by chronic infection from one of two viruses: hepatitis B or hepatitis C. Alcohol abuse also increases the risk of developing cirrhosis. Some inherited diseases, especially a disorder called hemochromatosis (in which the body absorbs too much iron, which gets deposited in liver among other organs), can cause cirrhosis and, in time, hepatocellular carcinoma, as can non-alcoholic steatohepatitis (NASH), which is fat deposition in the liver, along with inflammation and damage.
If you have chronic liver infection or damage and your AFP suddenly rises, or if it is very elevated, your healthcare practitioner will usually ask for a study to look at your liver, such as an ultrasound exam, a CT scan, an MRI scan, or a biopsy for histopathological evaluation of tumor tissues. The scans can usually spot liver cancers if they are present. Your healthcare practitioner may also order a blood test for des-gamma carboxy prothrombin (DCP), which is also known as prothrombin induced by vitamin K absence-II (PIVKA-II), to help detect and monitor liver cancer.
AFP is not available as a home test and it is not typically performed in a healthcare practitioner's office. Testing is done by either a hospital laboratory or a reference laboratory.
Sources Used in Current Review
(2019 April 9, Updated). Testicular Cancer Treatment (PDQ) – Patient Version. National Cancer Institute. Available online at https://www.cancer.gov/types/testicular/patient/testicular-treatment-pdq. Accessed July 2020.
Cicalese, L. (2019 May 13, Updated). Hepatocellular Carcinoma. Medscape General Surgery. Available online at https://emedicine.medscape.com/article/197319-overview. Accessed July 2020.
Adkins, E. S. (2019 July 31, Updated). Pediatric Teratomas and Other Germ Cell Tumors. Medscape Pediatrics: Surgery. Available online at https://emedicine.medscape.com/article/939938-overview. Accessed July 2020.
Genzen, J. (2019 October, Updated). Testicular Cancer. ARUP Consult. Available online at https://arupconsult.com/content/testicular-cancer?_ga=2.268908914.2056076676.1573304696-1793245273.1560683717. Accessed July 2020.
Genzen, J. and Miles, R. (2019 October, Updated). Hepatocellular Carcinoma – HCC. ARUP Consult. Available online at https://arupconsult.com/content/hepatocellular-carcinoma?_ga=2.254743051.2056076676.1573304696-1793245273.1560683717. Accessed July 2020.
(2019 July 2, Updated). Adult Primary Liver Cancer Treatment (PDQ) – Patient Version. National Cancer Institute. Available online at https://www.cancer.gov/types/liver/patient/adult-liver-treatment-pdq. Accessed July 2020.
(© 1995–2019). Alpha-Fetoprotein (AFP) Tumor Marker, Serum. Mayo Clinic Laboratories. Available online at https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/8162. Accessed July 2020.
Mulcahy, N. (2019 May 13). FDA Approves First Biomarker-Driven Drug for HCC. Medscape Medical News, FDA Approvals. Available online at https://www.medscape.com/viewarticle/912935. Accessed July 2020.
(2019 February 4, Updated). Alpha Fetoprotein (AFP) Tumor Marker Test. MedlinePlus. Available online at https://medlineplus.gov/lab-tests/alpha-fetoprotein-afp-tumor-marker-test/. Accessed July 2020.
Frenette, C. et. al. (2019 September). A Practical Guideline for Hepatocellular Carcinoma Screening in Patients at Risk. Mayo Clin Proc Innov Qual Outcomes. 2019 Sep; 3(3): 302–310. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713857/. Accessed July 2020.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Sherman, M. (2005 June 23). Hepatocellular Carcinoma: Epidemiology, Risk Factors, and Screening. Medscape, from Semin Liver Dis. 2005;25(2):143-154 [On-line information]. Available online at http://www.medscape.com/viewarticle/506830.
(2005 January 05). LBA AFP-L3. Wako [On-line package insert]. PDF available for download at http://liver.wakousa.com/pdfs/packageinsert.pdf.
Hepatocellular Carcinoma: Alpha Fetoprotein. Specialty Laboratories [On-line information]. Available online at http://www.specialtylabs.com/books/display.asp?id=529.
Grund, S. (2004 August 10, Updated). Hepatocellular Carcinoma. MedlinePlus, Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000280.htm.
(2005 April 14, Modified). Hepatocellular Cancer (PDQ®): Screening Health Professional Version. National Cancer Institute [On-line information]. Available online at http://www.cancer.gov/cancertopics/pdq/screening/hepatocellular/healthprofessional/allpages.
(© 2003). Alpha-Fetoprotein (AFP) with AFP L3%, Serum. Laboratory Corporation of America [On-line test information]. Available online at http://www.labcorp.com/datasets/labcorp/html/chapter/mono/nf10005300.htm.
Wako Diagnostics Receives the FDA Approval for a New Biomarker for Liver Cancer. Press Release, Richmond VA USA -- Medical Industry E-mail News Service(TM) -- June 21, 2005.
Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 47-49.
Clarke, W. and Dufour, D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 271-272.
(2008 March). Germ Cell Tumors – Childhood. Cancer.Net [On-line information] Available online at http://www.cancer.net/patient/Cancer+Types/Germ+Cell+Tumor+-+Childhood. Accessed May 2009.
Vorvick, L. (2008 October 28). Alpha fetoprotein. MedlinePlus Medical Encyclopedia [On-line information] Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003573.htm. Accessed May 2009.
(Revised 2009 May 06). Overview: Liver Cancer, How Is Liver Cancer Found? American Cancer Society [On-line information]. Available online at http://www.cancer.org/docroot/cri/content/cri_2_2_3x_how_is_liver_cancer_found_25.asp. Accessed May 2009.
(Modified 2009 May 22). Adult Primary Liver Cancer Treatment (PDQ®) National Cancer Institute [On-line information]. Available online at http://www.cancer.gov/cancertopics/pdq/treatment/adult-primary-liver/HealthProfessional/page1. Accessed May 2009.
(Revised 2009 May 14). Detailed Guide: Testicular Cancer, How Is Testicular Cancer Diagnosed? American Cancer Society [On-line information]. Available online at http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_testicular_cancer_diagnosed_41.asp?sitearea=ped. Accessed May 2009.
(Revised 2008 December 08). Tumor Markers, What are tumor markers? American Cancer Society [On-line information]. Available online at http://www.cancer.org/docroot/PED/content/PED_2_3X_Tumor_Markers.asp?sitearea=PED. Accessed May 2009.
Walzer, N. and Kulik, L. (2008 June 10). Hepatocellular Carcinoma: Latest Developments. Medscape from Current Opinion in Gastroenterology [On-line information]. Available online at http://www.medscape.com/viewarticle/573576. Accessed May 2009.
(2007 November). AFP-L3% in Serum (Includes Total Alpha Fetoprotein). ARUP Technical Bulletin [On-line information]. Available online through http://www.aruplab.com. Accessed May 2009.
(Revised 2012 October 5). Ovarian Cancer. American Cancer Society [On-line information]. Available online at http://www.cancer.org/cancer/ovariancancer/detailedguide/index. Accessed October 2012.
(Updated 2012 May 14). Stuart, K. and Stadler, Z. Primary Hepatic Carcinoma. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/282814-overview. Accessed October 2012.
(© 1995-2012). Alpha-Fetoprotein (AFP) Tumor Marker, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/8162. Accessed October 2012.
Grenache, D. and Jarboe, E. (Updated 2011 May). Hepatocellular Carcinoma. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/HepatocellularCarcinoma.html?client_ID=LTD. Accessed October 2012.
(Updated 2012 August 1). Fazal Hussain, F. and Homoud, H. Gynecologic Tumor Markers Tumor Marker Overview. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/269839-overview. Accessed October 2012.
Grenache, D. et. al. (Updated 2012 May). Ovarian Cancer. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/OvarianCancer.html?client_ID=LTD. Accessed October 2012.
Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 42-44.
Clarke, W., Editor (© 2011). Contemporary Practice in Clinical Chemistry 2nd Edition: AACC Press, Washington, DC. Pp 486, 496, 499.
(January 2011) Bruix J, Sherman M. Management of Hepatocellular Carcinoma. American Association for the Study of Liver Diseases Practice Guideline. Hepatology Vol. 53, No. 3, 2011. PDF available for download at http://www.aasld.org/practiceguidelines/documents/bookmarked%20practice%20guidelines/hccupdate2010.pdf. Accessed November 2012.
(December 2011) Llovet J, et al. Clinical Practice Guidelines: Management of hepatocellular carcinoma. European Association for the Study of the Liver and European Organisation for Research and Treatment of Cancer. Journal of Hepatology 2012 vol. 56 j 908–943. PDF available for download at http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf. Accessed November 2012.
Abdel B Halim, PharmD, PhD, DABCC, FACB, VP Translational Medicine, Biomarkers and Diagnostics.
(May 2014) Nonalcoholic steatohepatitis. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Available online at http://www.niddk.nih.gov/health-information/health-topics/liver-disease/nonalcoholic-steatohepatitis/Pages/facts.aspx. Accessed on 02/06/2016.
Serum Des-Gamma-Carboxy Prothrombin (DCP). Mayo Clinic. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/61844. Accessed on 02/06/2016.
Choi JY et al. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 2013 Jan 21; 19(3): 339–346. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554817/. Accessed 02/06/2016.
Kudo M. Clinical Practice Guidelines for Hepatocellular Carcinoma Differ between Japan, United States, and Europe. Liver Cancer. 2015 Mar; 4(2): 85–95. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439783/. Accessed Feb 2016.