Alpha Fetoprotein (AFP)

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

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.¹ 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.¹
  • Gastric cancer
  • Biliary tract cancer
  • Pancreatic cancer
• Cirrhosis: patients may have abnormal AFP values, although usually less than 500 ng per mL.
• Viral hepatitis
• Ataxia telangiectasia
• Pregnancy:
  • Maternal serum AFP test results are interpreted according to the gestational age are often reported in terms of multiple of the median (MoM). Because the median is calculated from tests of other women's pregnancies at the same gestational age, in effect MoM is independent of gestational age. A typical normal range is 0.5 to 2.0 or 2.5 MoM.
  • Is associated with elevated AFP levels, particularly if the pregnancy is complicated by a spinal cord defect or other abnormality.¹
  • 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.²
  • Where AFP levels are raised but there is no fetal abnormality, there may be greater risk of obstetric complications.³

Screening for neural tube defects and trisomy

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

• Open neural tube defects (ONTD) e.g. spina bifida
• Down's syndrome
• Chromosomal abnormalities e.g. trisomy 18⁴
• Defects in the abdominal wall of the fetus - omphalocoele

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.⁵

Hepatocellular carcinoma (HCC)

Chronic hepatitis B infection may cause HCC. AFP and liver ultrasound are used to screen these patients for HCC. A Cochrane review concluded that it is uncertain whether screening is worthwhile.⁶ 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.^7,8

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.¹

Acute liver failure

Serum concentrations of 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.⁹

Diagnostic aid in premature rupture of membranes

A recent study looked at prolactin, 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.¹⁰