From the Guidelines
Elevated alpha-fetoprotein (AFP) levels are most concerning for liver cancer (hepatocellular carcinoma) and certain germ cell tumors, but can also be caused by pregnancy, liver diseases, and non-cancerous conditions. Elevated AFP levels can be indicative of various conditions, including liver cancer, germ cell tumors, pregnancy, liver diseases such as cirrhosis, hepatitis, and liver damage, as well as non-cancerous conditions like ataxia-telangiectasia and hereditary tyrosinemia 1. The degree of elevation often correlates with the underlying cause, with modest elevations commonly seen in benign liver conditions and significant elevations more concerning for malignancy 1. When elevated AFP is detected, further diagnostic workup typically includes imaging studies like ultrasound, CT, or MRI of the liver, and possibly tissue biopsy depending on the clinical context 1. High serum levels of AFP are associated with biologically aggressive HCC and correlated with histoprognostic factors, including microscopic vascular invasion and poor differentiation 1. It is essential to consider the clinical context and use AFP levels in conjunction with other diagnostic tools to guide patient management, as the presence of normal levels of AFP or other serum biomarkers does not rule out HCC aggressiveness or worse outcomes 1. Key points to consider when evaluating elevated AFP levels include:
- Liver cancer (hepatocellular carcinoma) and germ cell tumors are the most concerning causes of elevated AFP
- Pregnancy, liver diseases, and non-cancerous conditions can also cause elevated AFP levels
- The degree of elevation correlates with the underlying cause
- Imaging studies and tissue biopsy may be necessary for further diagnostic workup
- High serum levels of AFP are associated with biologically aggressive HCC and poor prognosis 1.
From the Research
Elevated AFP Causes
Elevated alpha-fetoprotein (AFP) levels can be caused by various factors, including:
- Hepatocellular carcinoma (HCC) 2, 3, 4
- Chronic hepatitis C (CHC) 5
- Chronic active hepatitis 3
- Alcoholic cirrhosis 3
- Acute viral hepatitis 3
- Liver disease with viral etiology 2
- Cirrhosis 2
- Elevated alanine aminotransferase level 2
- Low albumin level 2
- HCC tumor size >2 cm 2
- Multinodular HCC 2
- Vascular invasion 2
Non-HCC Related Elevated AFP
Elevated AFP levels can also be found in patients without HCC, such as:
- Patients with chronic hepatitis C and stage III/IV hepatic fibrosis 5
- Patients with acute viral hepatitis 3
- Patients receiving interferon therapy for HCV 6
Clinical Significance
Elevated AFP levels can have clinical significance, including: