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Alpha-fetoprotein (AFP)
(Oncofetal Glycoprotein – Tumor Marker & Prenatal Screening Marker)
Synonyms
- AFP
- Alpha-fetoprotein
- α-Fetoprotein
- Oncofetal antigen
- Fetal albumin-like protein
Units of Measurement
µg/L, ng/L, ng/dL, ng/100mL, ng%, ng/mL, IU/mL
(Most common: ng/mL or IU/mL for tumor marker use)
Description
Alpha-fetoprotein (AFP) is a glycoprotein primarily produced by:
- Fetal liver
- Yolk sac
- GI tract of the fetus
AFP levels are high in fetal life and fall rapidly after birth, becoming very low in healthy adults.
AFP is a key biomarker for:
- Hepatocellular carcinoma (HCC)
- Germ cell tumors (yolk sac tumors)
- Prenatal screening (neural tube defects, Down syndrome)
- Chronic liver disease monitoring
Physiological Role
- Fetal transport protein (similar to albumin)
- Regulates fetal immune system development
- Binds estrogens and fatty acids in fetal circulation
- Protects fetus from maternal immune responses
In adults, AFP has no significant physiological role.
Clinical Significance
Elevated AFP in Adults
1. Hepatocellular Carcinoma (HCC)
AFP is a key tumor marker.
- AFP > 400 ng/mL → strongly suggestive of HCC
- AFP 20–200 ng/mL → possible HCC; requires imaging
- Sensitivity improves when combined with ultrasound & DCP (PIVKA-II)
2. Germ Cell Tumors
Especially non-seminomatous tumors:
- Yolk sac tumor
- Embryonal carcinoma
- Mixed germ cell tumors
AFP helps:
- Diagnose
- Stage
- Monitor treatment
- Detect relapse
3. Chronic Liver Disease
Moderate elevations seen in:
- Cirrhosis
- Chronic hepatitis B
- Chronic hepatitis C
- Alcoholic liver disease
- NAFLD/NASH
Another surge in AFP in cirrhosis may indicate transformation to HCC.
Elevated AFP in Pregnancy
AFP is used in maternal serum screening (15–20 weeks).
High AFP:
- Neural tube defects (spina bifida, anencephaly)
- Abdominal wall defects
- Multiple gestation
- Fetal demise
Low AFP:
- Down syndrome (Trisomy 21)
- Trisomy 18
- Incorrect gestational dating
Low AFP in Adults
Not clinically relevant (AFP normally low in adults).
Reference Intervals
(Tietz 8E + Mayo + AASLD + IFCC + ARUP)
Adults
- < 10 ng/mL
- ≈ < 10 µg/L
- < 10 IU/mL (assay dependent)
Pregnancy (Maternal Serum AFP)
- Increases from 15–20 weeks
- Peak ≈ 400–500 ng/mL (gestation dependent)
Infants
| Age | AFP Level |
| Birth | 30,000–100,000 ng/mL |
| 1 month | ~1,000–10,000 ng/mL |
| 6–12 months | Approaches adult range |
| >1 year | Adult reference (<10 ng/mL) |
(Extremely high AFP in infants can indicate hepatoblastoma.)
AFP in HCC Screening
Per AASLD hepatocellular carcinoma guidelines:
- AFP >20 ng/mL → suspicious
- AFP >200–400 ng/mL → highly suggestive of HCC in at-risk adults
- Use together with ultrasound every 6 months
- DCP (PIVKA-II) combination improves sensitivity
Unit Meanings
| Unit | Meaning |
| µg/L | microgram per liter |
| ng/L | nanogram per liter |
| ng/mL | nanogram per milliliter |
| ng/dL | nanogram per deciliter |
| ng/100 mL | ng% |
| ng% | nanogram per 100 mL |
| IU/mL | international units per milliliter (assay specific) |
Analytical Notes
- AFP is measured using immunoassays, chemiluminescent or ELISA.
- Biological variation is common in chronic liver disease; interpret trends, not isolated values.
- Always correlate AFP with liver imaging in HCC screening.
- False positives can occur in:
- Pregnancy
- Active hepatitis
- Liver regeneration
- Pregnancy
Clinical Pearls
- AFP alone is not sufficient to diagnose HCC - must combine with imaging.
- AFP can be normal in up to 40% of HCC cases (especially small tumors).
- AFP >1000 ng/mL → often indicates advanced HCC or yolk sac tumor.
- AFP is essential for tumor monitoring post-treatment.
- In neonates, AFP is normally extremely high — do not misinterpret.
Interesting Fact
AFP was one of the first recognized tumor markers, discovered in 1956. Its structure resembles albumin, making it a “fetal version” of albumin during development.
References
- Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Tumor Markers.
- AASLD Guidelines - Hepatocellular Carcinoma Screening & AFP.
- Mayo Clinic Laboratories - AFP Test Catalog.
- ARUP Consult - AFP Interpretation.
- IFCC - Tumor Marker Standardization.
- MedlinePlus / NIH - AFP Overview.
- EASL Clinical Practice Guidelines - HCC Surveillance.