What is the clinical significance of an alpha-fetoprotein (AFP) level of 3.7 in a patient?

Clinical Significance of AFP Level 3.7

An AFP level of 3.7 ng/mL is within the normal adult reference range (typically <8-12 ng/mL) and has no concerning clinical significance in isolation. 1

Context-Dependent Interpretation

The clinical meaning of this AFP value depends entirely on the clinical context:

In Pregnancy Screening

• This value is completely normal for maternal serum AFP screening. 2 Prenatal screening for open neural tube defects uses cutoffs of 2.0-2.5 multiples of the median (MoM), not absolute values. 2 An AFP of 3.7 ng/mL in pregnancy would typically represent a normal MoM value depending on gestational age.
• Elevated AFP in pregnancy (>2.0-2.5 MoM) indicates risk for neural tube defects, with detection rates of 75-90% for open spina bifida and >95% for anencephaly. 2

In Hepatocellular Carcinoma (HCC) Surveillance

• This AFP level provides no diagnostic value for HCC and does not exclude the diagnosis. 1 The normal AFP range is 10-20 ng/mL, and your value of 3.7 falls well below this. 1
• Up to 35% of HCC cases present with completely normal AFP levels, even with large tumors. 1 In one large study of 1,158 HCC patients, 46% had AFP levels <20 ng/mL. 1
• AFP >200 ng/mL is required for diagnostic significance in HCC, with levels >400 ng/mL considered highly specific. 1, 3 Only 18% of HCC patients reach AFP >400 ng/mL. 1

Clinical Algorithm for HCC Risk Assessment

If this patient has cirrhosis or chronic liver disease:

• Continue surveillance with ultrasound every 6 months regardless of this normal AFP value. 2, 1
• The EASL guidelines specifically state that AFP combination with ultrasound is not recommended in Western populations due to the 80% increase in cost for only 6-8% improvement in detection. 2
• Imaging (ultrasound, CT, or MRI) is mandatory and cannot be replaced by AFP testing. 2, 3

If this patient has chronic hepatitis B:

• Asian guidelines and NCCN recommend combining ultrasound with AFP every 6 months specifically for HBsAg-positive patients. 1 However, this normal AFP value of 3.7 provides reassurance but does not eliminate the need for imaging surveillance.
• A rising AFP trend over time (even within normal range) is more concerning than a single value. 1

Important Clinical Pitfalls

• Never use AFP alone for HCC screening or diagnosis. 1, 3 The sensitivity is only 39-65% and specificity 76-97% depending on cutoff values. 3
• Do not assume normal AFP excludes HCC. 1 Two-thirds of HCCs <4 cm have AFP <200 ng/mL, and 20% of HCC patients never produce AFP. 1
• False positive AFP elevations occur with active hepatitis, cirrhotic regenerating nodules, pregnancy, and other malignancies. 1

Recommended Action

For a patient with liver disease risk factors and AFP 3.7:

• Proceed with standard imaging-based surveillance (ultrasound every 6 months for cirrhosis). 2, 1
• If imaging shows a suspicious lesion ≥1 cm with typical HCC features (arterial enhancement with washout), diagnosis can be made without biopsy regardless of AFP level. 3
• If imaging is atypical or non-diagnostic, proceed to biopsy. 3

For a pregnant patient with AFP 3.7:

• This is a normal value requiring no further action unless it represents an elevated MoM for gestational age. 2