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Alpha Fetoprotein (AFP)

This is the major protein of fetal serum, but it is usually undetectable after birth.1

Conditions which may have raised levels of Alpha Fetoprotein (AFP)

AFP elevations are associated with:

  • Hepatocellular carcinoma: AFP levels are abnormal in 80% patients, and exceed 1,000 ng per mL in 40 % patients with this cancer.2 The level may drop to normal after surgical resection.
  • Nonseminomatous germ cell tumours.
  • Gastrointestinal cancers: occasionally cause elevations of AFP, but rarely to greater than 1,000 ng per mL.2
  • Cirrhosis: patients may have abnormal AFP values, although usually less than 500 ng per mL.
  • Viral hepatitis
  • Ataxia telangiectasia
  • Pregnancy is associated with elevated AFP levels, particularly if the pregnancy is complicated by a spinal cord defect or other abnormality.2 Maternal serum containing above 2.5 times the normal median for weeks 16 to 18 of pregnancy has been detected in 88% of cases of anencephaly and in 79% of cases of open spina bifida.1
Weeks of pregnancy AFP In Serum ( IU /ml)
6-9 0-12
10-12 10-30
13-15 13-60
16-18 16-93
19-21 32-139
22-24 56-224
25-27 95-357
28-30 135-435
31-33 141-423
34-36 121-379
37 - 40 93-320
Uses

Screening for neural tube defects and trisomy

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

AFP is made by the yolk sac of the fetus, enters the amniotic fluid and crosses the placenta into the maternal circulation. Altered AFP levels, either too high or low compared to normal amounts, can indicate whether a woman is carrying a baby with a chromosome problem or certain birth defects. A pregnant woman's AFP levels decrease soon after birth. However, mid-trimester anomaly scanning may soon replace serum screening.4

Hepatocellular carcinoma (HCC)

Chronic hepatitis B infection may cause HCC. AFP and liver ultrasound are used to screen these patients for HCC. A recent Cochrane review concluded that it is uncertain whether screening is worthwhile.5 The use of AFP in hepatocellular carcinoma screening continues to be debated. Retrospective studies in Asia showed improved survival with AFP screening, but the findings of this study have not been duplicated.6 7

Cirrhosis

Some experts use annual AFP and ultrasound screening in patients with well-compensated non alcohol-induced cirrhosis. In patients with a hepatic mass and risk factors for hepatocellular carcinoma, an AFP level above 500 ng per mL is often used instead of biopsy to diagnose hepatocellular carcinoma.2

Acute Liver Failure

Serum concentrations of alpha-fetoprotein (AFP), variably elevated during liver injury, have been suggested to be of prognostic importance in acute liver failure (ALF), higher values being associated with improved outcome. AFP values change dynamically during ALF. In a large prospective study, higher absolute values of AFP did not predict a favourable outcome, but a rising level of AFP over the first 3 hospital days frequently indicated survival.8

Diagnostic aid in Premature Rupture of Membranes

A recent study looked at prolactin, alpha-fetoprotein (AFP) and B-human chorionic gonadotropin (BHCG) as effective markers in vaginal fluid for diagnosing prelabour rupture of membranes (PROM). AFP had the greatest accuracy ( 94% sensitivity and specificity), and could be an ideal marker for diagnosing PROM in equivocal cases.9


Document References
  1. Waldmann, T.A. and McIntire, K.R.; DRG AFP MTPL Enzymeimmunoassay for the quantitative determination of Alpha-Fetoprotein (AFP) in serum and amniotic fluid.
  2. Johnson PJ; The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis. 2001 Feb;5(1):145-59. [abstract]
  3. Lindenbaum RH, Ryynanen M, Holmes-Siedle M, et al; Trisomy 18 and maternal serum and amniotic fluid alpha-fetoprotein. Prenat Diagn. 1987 Sep;7(7):511-9. [abstract]
  4. Kooper AJ, de Bruijn D, van Ravenwaaij-Arts CM, et al; Fetal anomaly scan potentially will replace routine AFAFP assays for the detection of neural tube defects. Prenat Diagn. 2007 Jan;27(1):29-33. [abstract]
  5. Wun YT, Dickinson JA. Alpha-fetoprotein and/or liver ultrasonography for liver cancer screening in patients with chronic hepatitis B. Cochrane Review.; November, 2002
  6. Tang ZY, Yu YQ, Zhou XD, et al; Subclinical hepatocellular carcinoma: an analysis of 391 patients. J Surg Oncol Suppl. 1993;3:55-8. [abstract]
  7. Yuen MF, Cheng CC, Lauder IJ, et al; Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience. Hepatology. 2000 Feb;31(2):330-5. [abstract]
  8. Schiodt FV, Ostapowicz G, Murray N, et al; Alpha-fetoprotein and prognosis in acute liver failure. Liver Transpl. 2006 Dec;12(12):1776-81. [abstract]
  9. 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. [abstract]
Acknowledgements EMIS is grateful to Dr Hayley Willacy for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2007.
DocID: 3177
Document Version: 20
DocRef: bgp25951
Last Updated: 4 Jan 2007
Review Date: 3 Jan 2009
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