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Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Down's syndrome screening article more useful, or one of our other health articles.

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What is alpha-fetoprotein (AFP)?

Alpha-fetoprotein (AFP) is the major protein of fetal serum but it is usually undetectable after birth. AFP is made by the yolk sac of the fetus, enters the amniotic fluid and crosses the placenta into the maternal circulation. See also the separate Tumour Markers article.

Conditions which may lead to raised levels of alpha-fetoprotein

  • Hepatocellular carcinoma (HCC): AFP levels are abnormal in 40-60% of patients. The American Association for the Study of Liver Diseases recommends diagnosis of HCC in patients with cirrhosis in the presence of a mass in the liver if AFP is >200 ng/mL1 .

  • Other gastrointestinal cancers:

  • Nonseminomatous germ cell tumours: if suspected, AFP measurement is essential3 .

  • Alpha-fetoprotein may also be raised in patients with metastatic lung cancer and (rarely) primary lung cancer4 .

  • Cirrhosis: patients may have abnormal AFP values, although usually less than 500 ng/mL.

  • Viral hepatitis.

  • Ataxia with telangiectasia5 .

  • Pregnancy is associated with elevated AFP levels, particularly if the pregnancy is complicated by a spinal cord defect or other abnormality:

    • Maternal serum AFP test results, interpreted according to the gestational age. See also the articles on Prenatal Diagnosis and Neural Tube Defects.

    • Raised levels of maternal AFP at 16-18 weeks of gestation are found in fetal neural tube defects6 .

    • Amniotic fluid AFP and acetylcholinesterase concentrations can be used to differentiate between open ventral wall defects (gastroschisis and omphalocele) and open neural tube defects7 .

    • Where there are high levels of AFP levels but there is no fetal abnormality, there may be greater risk of obstetric complications8 .

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Uses of alpha-fetoprotein measurement

Screening for neural tube defects and trisomy

See also the separate Prenatal Diagnosis and Prenatal Screening for Down's Syndrome articles.

AFP screening is a simple maternal blood test, performed at around 15 weeks of gestation, that can detect increased risk to the fetus of certain genetic abnormalities such as:

  • Open neural tube defects - eg, spina bifida.

  • Down's syndrome9 .

  • Other chromosomal abnormalities - eg, trisomy 1810 .

  • Defects in the abdominal wall of the fetus - omphalocele.

A pregnant woman's AFP levels decrease soon after birth.

Diagnostic aid in premature rupture of membranes (PROM)

A study looking at prolactin, AFP and beta human chorionic gonadotrophin (beta-hCG) in vaginal fluid as markers for diagnosing PROM, showed that AFP had the greatest accuracy (94% sensitivity and specificity)11 . Further studies have confirmed the reliability of cervicovaginal AFP for diagnosing PROM in equivocal cases12 .

Altered AFP levels, either too high or low compared with normal amounts, can also indicate increased risk of obstetric problems such as placenta accreta/increta/percreta when placenta praevia has been diagnosed13 .

Hepatocellular carcinoma (HCC)

Chronic hepatitis B and C infection may cause HCC. In conjunction with abdominal ultrasonography, AFP can be measured at six-monthly intervals in such patients who are at high risk of HCC (especially those with liver cirrhosis related to hepatitis B or C). However, a Cochrane review concluded that there is not enough evidence to know whether screening is worthwhile14 . A Health Technology Assessment concluded that the most effective surveillance strategy is to screen high-risk patients with both AFP assay and ultrasound imaging on a six-monthly basis. However, the addition of ultrasound is only cost-effective in those with blood AFP level >20 ng/mL15 .

Acute liver failure

Serum concentrations of AFP that are variably elevated during liver injury have been suggested to be of prognostic importance in acute liver failure, with higher values being associated with improved outcome. AFP values change dynamically during acute liver failure. In a large prospective study, higher absolute values of AFP did not predict a favourable outcome; however, a rising level of AFP over the first three hospital days frequently indicated survival16 .

Further reading and references

  1. Beale G, Chattopadhyay D, Gray J, et al; AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease. BMC Cancer. 2008 Jul 18;8:200. doi: 10.1186/1471-2407-8-200.
  2. Chun H, Kwon SJ; Clinicopathological characteristics of alpha-fetoprotein-producing gastric cancer. J Gastric Cancer. 2011 Mar;11(1):23-30. doi: 10.5230/jgc.2011.11.1.23. Epub 2011 Mar 31.
  3. Sturgeon CM, Lai LC, Duffy MJ; Serum tumour markers: how to order and interpret them. BMJ. 2009 Sep 22;339:b3527. doi: 10.1136/bmj.b3527.
  4. Kitada M, Ozawa K, Sato K, et al; Alpha-fetoprotein-producing primary lung carcinoma: a case report. World J Surg Oncol. 2011 May 9;9:47. doi: 10.1186/1477-7819-9-47.
  5. Stray-Pedersen A, Borresen-Dale AL, Paus E, et al; Alpha fetoprotein is increasing with age in ataxia-telangiectasia. Eur J Paediatr Neurol. 2007 Nov;11(6):375-80. Epub 2007 May 30.
  6. Krantz DA, Hallahan TW, Sherwin JE; Screening for open neural tube defects. Clin Lab Med. 2010 Sep;30(3):721-5. Epub 2010 Jun 15.
  7. Yoon CH, Kang SK, Jin CH, et al; A meningomyelocele with normal intracranial signs on ultrasound and false-negative amniotic fluid alpha-fetoprotein and acetylcholinesterase. Obstet Gynecol Sci. 2014 May;57(3):223-7. doi: 10.5468/ogs.2014.57.3.223. Epub 2014 May 15.
  8. Chandra S, Scott H, Dodds L, et al; Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes. Am J Obstet Gynecol. 2003 Sep;189(3):775-81.
  9. Canick JA, MacRae AR; Second trimester serum markers. Semin Perinatol. 2005 Aug;29(4):203-8.
  10. Huang T, Alberman E, Wald N, et al; Triploidy identified through second-trimester serum screening. Prenat Diagn. 2005 Mar;25(3):229-33.
  11. Shahin M, Raslan H; Comparative Study of Three Amniotic Fluid Markers in Premature Rupture of Membranes: Prolactin, Beta Subunit of Human Chorionic Gonadotropin, and Alpha-Fetoprotein. Gynecol Obstet Invest. 2006 Dec 7;63(4):195-199.
  12. Singh CR, Bhat RG; Alpha-foetoprotein in the diagnosis of prelabour rupture of membranes. J Clin Diagn Res. 2014 Nov;8(11):OC01-2. doi: 10.7860/JCDR/2014/8259.5093. Epub 2014 Nov 20.
  13. Gagnon A, Wilson RD, Audibert F, et al; Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008 Oct;30(10):918-49.
  14. Aghoram R, Cai P, Dickinson JA; Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B. Cochrane Database Syst Rev. 2012 Sep 12;9:CD002799. doi: 10.1002/14651858.CD002799.pub2.
  15. Thompson Coon J, Rogers G, Hewson P, et al; Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis. Health Technol Assess. 2007 Sep;11(34):1-206.
  16. Schiodt FV, Ostapowicz G, Murray N, et al; Alpha-fetoprotein and prognosis in acute liver failure. Liver Transpl. 2006 Dec;12(12):1776-81.

Article history

The information on this page is written and peer reviewed by qualified clinicians.

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