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Alpha-1-Fetoprotein (AFP) – Tumor Marker and Prenatal Testing

Alpha-1-fetoprotein (AFP) is a blood protein used as a tumor marker and in prenatal diagnostics. Elevated levels may indicate liver disease or certain types of cancer.

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Things worth knowing about "Alpha-1-Fetoprotein"

Alpha-1-fetoprotein (AFP) is a blood protein used as a tumor marker and in prenatal diagnostics. Elevated levels may indicate liver disease or certain types of cancer.

What is Alpha-1-Fetoprotein?

Alpha-1-fetoprotein (AFP) is a glycoprotein -- a protein molecule with attached sugar chains. It is primarily produced in the liver and gastrointestinal tract of the developing fetus. In healthy adults, AFP levels in the blood are very low. However, elevated levels can indicate specific medical conditions, making AFP a valuable diagnostic marker in clinical practice.

Biological Function

In the fetus, AFP serves a function similar to that of albumin in adults: it transports fatty acids, hormones, and other substances through the bloodstream. It also plays a role in modulating the immune system during pregnancy, helping to prevent the maternal immune system from rejecting the fetus. After birth, AFP levels rapidly decline and reach normal adult levels within the first few months of life.

Clinical Significance as a Tumor Marker

In adults, AFP is primarily used as a tumor marker. Significantly elevated AFP levels in the blood may indicate the following conditions:

Hepatocellular carcinoma (HCC): Primary liver cell cancer is the most common cause of markedly elevated AFP levels in adults.
Germ cell tumors: Certain tumors of the testes or ovaries (e.g., non-seminomatous germ cell tumors) also produce AFP.
Liver metastases: Secondary tumors that have spread to the liver can also raise AFP levels.
Benign liver diseases: Conditions such as liver cirrhosis, chronic hepatitis B or C may cause mildly to moderately elevated AFP values.

Use in Prenatal Diagnostics

Another key application of AFP is in prenatal screening. AFP is measured in the maternal blood and in amniotic fluid to assess the risk of certain fetal developmental abnormalities:

Elevated AFP levels in amniotic fluid or maternal blood may indicate open neural tube defects (e.g., spina bifida), abdominal wall defects, or other fetal malformations.
Low AFP levels, in combination with other markers (triple or quadruple test), may suggest an increased risk of trisomy 21 (Down syndrome).

AFP is part of the so-called first-trimester screening and the multiple marker test, typically performed between the 15th and 20th week of pregnancy. An abnormal result does not necessarily confirm a diagnosis but calls for further diagnostic evaluation.

Diagnosis and Measurement

AFP levels are measured from a simple blood sample (venous blood draw). The normal reference value in non-pregnant adults is generally below 10 ng/mL (nanograms per milliliter), though this may vary slightly between laboratories. When interpreting results, factors such as age, sex, pregnancy status, and underlying medical conditions must always be taken into account.

When Should AFP Be Tested?

Suspected hepatocellular carcinoma (e.g., in patients with known liver cirrhosis or chronic viral hepatitis)
Monitoring of known AFP-producing tumors during and after treatment
Prenatal screening to assess the risk of fetal abnormalities
Follow-up care after treatment of germ cell tumors

Limitations of the AFP Test

AFP is not a specific marker for a single disease. Elevated values can have multiple causes, which is why the test result must always be interpreted alongside clinical findings, imaging studies (e.g., ultrasound, MRI), and other laboratory values. A normal AFP level does not reliably exclude a malignancy.

References

European Association for the Study of the Liver (EASL): Clinical Practice Guidelines on the management of hepatocellular carcinoma. Journal of Hepatology, 2018. DOI: 10.1016/j.jhep.2018.03.019
American College of Obstetricians and Gynecologists (ACOG): Prenatal Diagnostic Testing for Genetic Disorders. Practice Bulletin No. 162, 2016.
Schwartz, J.M. & Carithers, R.L.: Epidemiology and etiologic associations of hepatocellular carcinoma. UpToDate, Wolters Kluwer, 2023.

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