From the Guidelines
Elevated Alpha-fetoprotein (AFP) levels are primarily associated with liver cancer (hepatocellular carcinoma), as well as other liver conditions such as cirrhosis, hepatitis, and liver metastases from other cancers, and certain germ cell tumors like testicular cancer and some ovarian cancers. The most recent and highest quality study, published in 2025 1, highlights the significance of AFP in the management of hepatocellular carcinoma (HCC), indicating that high serum levels of AFP are associated with biologically aggressive HCC and correlated with histoprognostic factors, including microscopic vascular invasion and poor differentiation. Some key points to consider include:
- Elevated AFP levels can also be seen in benign liver diseases, but significant elevations are more strongly suggestive of malignancy.
- During pregnancy, abnormally high maternal serum AFP may suggest neural tube defects, multiple pregnancies, or certain chromosomal abnormalities.
- The degree of AFP elevation often correlates with the underlying condition, with mild elevations commonly seen in benign liver diseases and significant elevations more strongly suggesting malignancy.
- When elevated AFP is detected, further diagnostic testing is typically needed, including imaging studies like ultrasound, CT, or MRI to evaluate the liver and, in males, the testes.
- Other conditions that can cause elevated AFP levels include certain germ cell tumors, such as testicular cancer and some ovarian cancers, as well as liver metastases from other cancers.
- The biological reason for AFP elevation is that these pathological conditions either damage liver cells, causing AFP release, or involve cells that abnormally produce AFP as part of their malignant transformation, as noted in a study from 2021 1. It's also worth noting that while AFP is a useful marker for HCC, it is not diagnostic on its own and should be used in conjunction with other diagnostic tests, such as imaging studies, to confirm a diagnosis of HCC, as recommended in a study from 2012 1.
From the Research
Conditions Associated with Elevated Alpha-fetoprotein (AFP) Levels
Elevated Alpha-fetoprotein (AFP) levels are associated with several conditions, including:
Hepatocellular Carcinoma (HCC) and AFP
HCC is a major type of primary liver cancer and a major cause of cancer-related deaths worldwide 4. Elevated AFP levels are found in 60-70% of patients with HCC 3. The progressive elevation of AFP levels can be used for the diagnosis of HCC in patients with liver cirrhosis 3. High AFP expression is associated with unfavorable prognosis, vascular invasion, higher tumor grade, and macrotrabecular-massive tumor subtype 5.
Clinical Characteristics and Outcomes
Patients with HCC can be classified as AFP-negative or AFP-positive based on their serum AFP levels 6. AFP-positive patients have worse prognosis, larger tumor size, more lymph node metastasis, and distant metastasis compared to AFP-negative patients 6. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates are significantly better in AFP-negative patients compared to AFP-positive patients 6.
AFP as a Diagnostic and Prognostic Marker
AFP is the most widely used diagnostic and prognostic serum biomarker for HCC 5. However, approximately 30% of HCC patients do not exhibit abnormal serum AFP levels at the time of diagnosis 6. The serum AFP concentration is an independent prognostic parameter and represents a more robust prognostic predictor compared to AFP immunostaining of core biopsies 5.