AFP (Alpha-Fetoprotein) Test – Meaning, Function, Normal Range, and Clinical Importance

Introduction

Alpha-Fetoprotein (AFP) is a very important protein that plays a major role during fetal development and later serves as a key diagnostic marker in adults. It is mainly used to detect liver cancer, certain germ cell tumors, and abnormalities during pregnancy. The AFP test helps doctors understand liver health, detect tumors, and screen for fetal developmental disorders.

What is AFP (Alpha-Fetoprotein)?

AFP (Alpha-Fetoprotein) is a protein naturally produced by the liver and yolk sac of a developing fetus. In a normal healthy adult, AFP levels are very low or almost undetectable.
However, when liver cells become damaged or cancerous, they may start producing AFP again — a process known as re-expression. Because of this, AFP serves as an important tumor marker in adults.

Clinical Importance

• Used in the diagnosis and monitoring of liver cancer (Hepatocellular carcinoma or HCC).
• Helps detect germ cell tumors of the testis and ovaries.
• During pregnancy, AFP is used in maternal blood screening to check the risk of fetal abnormalities such as neural tube defects (like spina bifida) and chromosomal disorders (like Down syndrome).

Where is AFP Produced in the Body?

In Fetuses:

• The fetal liver and yolk sac are the main sources of AFP production.
• AFP circulates in the fetal bloodstream and passes in small amounts into the mother’s blood, which is why it can be measured during pregnancy.

In Adults:

• Normally, AFP levels are very low.
• However, AFP may be reproduced in the body in the following conditions:
  • Liver cancer or severe liver injury (Hepatocellular carcinoma).
  • Germ cell tumors of the testis or ovaries.
  • Certain benign (non-cancerous) liver conditions like hepatitis and cirrhosis.

Functions and Importance of AFP

In the Fetus:

• AFP acts like albumin, a protein that maintains osmotic balance and transports important molecules such as fatty acids, bilirubin, and hormones in the fetal blood.
• It helps regulate the exchange of fluids and nutrients between the mother and fetus.

In Adults (Clinical Importance):

1. Tumor Marker:
   • High AFP levels are strongly linked with hepatocellular carcinoma (liver cancer) and germ cell tumors.
   • Used to monitor response to cancer treatment and check for recurrence after therapy.
2. Liver Disease Marker:
   • AFP levels may rise in hepatitis B, hepatitis C, and cirrhosis due to liver cell damage, even without cancer.
3. Prenatal Screening:
   • AFP testing during pregnancy helps detect:
     • Neural tube defects (NTDs) such as spina bifida or anencephaly.
     • Down syndrome (Trisomy 21) and Edwards syndrome (Trisomy 18).
     • Multiple pregnancies or errors in estimating gestational age.

Causes of Low AFP Levels

During Pregnancy:

Low AFP in maternal serum may indicate:

• Down syndrome (Trisomy 21) – a genetic condition causing developmental delay.
• Trisomy 18 (Edwards syndrome) – a rare chromosomal disorder.
• Incorrect estimation of gestational age (if pregnancy is earlier than assumed).

In Non-Pregnant Adults:

• Low AFP is normal and does not have any clinical concern.

Symptoms of Low AFP

• Low AFP itself does not cause any symptoms.
• In pregnancy, low AFP levels may be a sign of chromosomal abnormalities in the fetus, which are identified through further diagnostic tests such as amniocentesis or ultrasound.

Causes of High AFP Levels

Cancer-Related Causes:

1. Hepatocellular Carcinoma (HCC):
   • The most common liver cancer that leads to a marked increase in AFP.
2. Testicular Germ Cell Tumors (Non-Seminomatous Type):
   • Tumors of the testis that often secrete AFP.
3. Ovarian Germ Cell Tumors:
   • Certain ovarian cancers also increase AFP.
4. Metastatic Liver Involvement:
   • Cancers spreading to the liver from other parts of the body.

Non-Cancerous (Benign) Causes:

• Chronic Hepatitis (B or C): Liver inflammation can mildly raise AFP.
• Liver Cirrhosis: Long-term liver scarring causes AFP production.
• Pregnancy: Naturally high AFP due to fetal production.
• Neonates (Newborns): AFP levels are normally high at birth and gradually decrease within one year.

During Pregnancy:

High maternal serum AFP levels may indicate:

• Neural tube defects (Spina bifida, Anencephaly).
• Multiple pregnancy (twins or triplets).
• Abdominal wall defects in the fetus.

Symptoms of High AFP Levels

AFP itself does not cause symptoms, but the underlying cause may show the following:

If due to Liver Cancer:

• Unexplained weight loss.
• Abdominal pain or swelling.
• Jaundice (yellowing of eyes and skin).
• Fatigue and loss of appetite.

If due to Liver Disease:

• Swelling of abdomen or legs.
• Dark urine, pale stool, or itching.
• Liver enlargement detected during physical examination.

If during Pregnancy:

• Abnormal AFP results may indicate possible fetal development issues, which are confirmed by ultrasound or amniocentesis.

Reference Ranges (Normal AFP Levels)

Group	Normal Range	Comments
Adults (non-pregnant)	< 10 ng/mL (some labs: < 20 ng/mL)	Normal levels
Pregnancy	Varies with gestational age (peaks around 15–20 weeks)	Used for fetal screening
Chronic liver disease (high risk for cancer)	> 400 ng/mL	Highly suggestive of liver cancer

Sample Type and Collection

• Sample Type: Blood serum
• Tube Used: Red-top (plain) tube
• Test Type: Blood test (no fasting required in most cases)

Test Preparation

• No special fasting or dietary restrictions are required before the AFP test.
• Inform your doctor if you are pregnant or have a known liver condition, as this affects result interpretation.
• In pregnancy, accurate gestational age estimation is important for proper AFP result analysis.

When to Consult a Doctor

You should consult a doctor if:

• You have chronic liver disease (hepatitis B/C or cirrhosis).
• You notice symptoms like jaundice, unexplained weight loss, or abdominal pain.
• You are pregnant and your AFP screening test shows abnormal results.
• You have a family history of liver cancer or testicular cancer.

Regular check-ups and early testing can help detect serious diseases early and improve treatment success.

Important Word Explanations

Word	Meaning
AFP (Alpha-Fetoprotein)	A protein made by the fetal liver; used as a tumor and prenatal marker.
Tumor Marker	A substance found in blood that helps detect or monitor cancer.
Hepatocellular Carcinoma (HCC)	The most common type of primary liver cancer.
Neural Tube Defects (NTDs)	Birth defects of the brain or spine, such as spina bifida.
Trisomy 21 / 18	Genetic conditions (Down syndrome and Edwards syndrome).
Cirrhosis	Long-term liver damage leading to scarring.
Amniocentesis	A test where fluid from the womb is taken to check fetal health.

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