From the Guidelines
A high AFP level is a concerning sign that may indicate liver cancer, particularly hepatocellular carcinoma (HCC), and warrants further diagnostic testing, including imaging studies like ultrasound, CT, or MRI, to examine the liver and other potentially affected organs. Alpha-fetoprotein (AFP) is a protein normally produced by the fetal liver that decreases after birth, so elevated levels in adults can indicate several concerning conditions. A high AFP level most commonly suggests liver cancer (hepatocellular carcinoma), certain testicular or ovarian germ cell tumors, or metastatic cancer [ 1 ]. During pregnancy, elevated AFP may indicate neural tube defects in the developing fetus, such as spina bifida or anencephaly. However, high AFP doesn't always mean cancer is present, as it can also be elevated in non-cancerous liver conditions like cirrhosis, hepatitis, or liver damage. Some key points to consider when evaluating a high AFP level include:
- The level of serum AFP may be elevated in those with certain nonmalignant conditions such as chronic HBV and HCV or be within normal limits in up to 30% patients with HCC [ 1 ].
- An imaging finding of classic enhancement is considered more definitive in the diagnostic setting compared with AFP level alone [ 1 ].
- Additional imaging studies (CT or MRI) are recommended for patients with a rising serum AFP level in the absence of a liver mass [ 1 ].
- If no liver mass is detected following measurement, biopsy may be considered when a lesion is suspicious for malignancy, but multiphasic CT or MRI results do not meet imaging criteria for HCC [ 1 ]. It's also worth noting that the normal range for AFP in non-pregnant adults is generally below 10 ng/mL, though reference ranges may vary slightly between laboratories. For adults with unexplained high AFP levels, further diagnostic testing is typically recommended to determine the underlying cause and guide management [ 1 ].
From the Research
Meaning of High AFP Level
A high Alpha-Fetoprotein (AFP) level can be indicative of various health issues. The following are some possible meanings of a high AFP level:
- Hepatocellular Carcinoma (HCC): A high AFP level can be a diagnostic criterion for HCC, with a threshold of 400 ng/mL showing better sensitivity and specificity than 200 ng/mL 2.
- Fetal Neural Tube Defects: Elevated AFP levels in maternal serum can be associated with fetal neural tube defects, as well as other congenital defects and genetic diseases 3.
- Testicular Cancer Recurrence: High AFP levels can be a marker for testicular cancer recurrence, although the sensitivity is often relatively low 4.
- Liver Regeneration: Elevated AFP levels can indicate active liver regeneration, which can be a sign of early recovery in acute viral hepatitis A 5.
- Other Disorders: High AFP levels can also be associated with other disorders, such as cirrhosis-related HCC, liver diseases, and fetal kidney diseases 6.
Possible Causes of Elevated AFP Levels
The following are some possible causes of elevated AFP levels:
- Fetal neural tube defects
- Congenital defects and genetic diseases
- Hepatocellular carcinoma
- Testicular cancer recurrence
- Liver regeneration
- Liver diseases
- Fetal kidney diseases
- Increased proteinuria in severe fetal kidney diseases
- Pathological overproduction in liver diseases
- Penetration through the membranes of gastrointestinal organs exposed to amniotic fluid
- Passage through the walls of skin vessels
- Hepatic hematopoiesis and increased transfer through the edematous placenta in fetal anemia 2, 3, 4, 6, 5