From the Guidelines
Elevation of the Alpha-Fetoprotein (AFP) marker can be caused by various conditions, including hepatocellular carcinoma, pregnancy, liver diseases, and certain cancers, as well as benign conditions like ataxia-telangiectasia and hereditary tyrosinemia. According to the most recent and highest quality study 1, an elevated AFP level can be indicative of hepatocellular carcinoma (HCC), particularly in patients with chronic HBV and HCV. Other cancers that can raise AFP include intrahepatic cholangiocarcinoma, some metastases from colon cancer, lymphoma, and germ cell tumors.
Causes of AFP Elevation
- Hepatocellular carcinoma (HCC)
- Pregnancy
- Liver diseases such as cirrhosis, hepatitis, and liver regeneration following injury
- Certain cancers, including intrahepatic cholangiocarcinoma, some metastases from colon cancer, lymphoma, and germ cell tumors
- Benign conditions like ataxia-telangiectasia and hereditary tyrosinemia
Clinical Considerations
It is essential to consider AFP results in conjunction with clinical context, imaging findings, and other laboratory tests, as an elevated AFP level can have various causes 1. The physiological basis for AFP elevation relates to its production by fetal liver cells, yolk sac, and gastrointestinal tract during development; when these cells are reactivated in disease states or when fetal development is abnormal, AFP levels increase in the bloodstream.
Diagnostic Approach
For accurate interpretation, AFP results should always be considered alongside clinical context, imaging findings, and other laboratory tests. 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.
From the Research
Causes of Elevation of Alpha-Fetoprotein (AFP) Marker
Elevation of the Alpha-Fetoprotein (AFP) marker can be caused by various factors, including:
- Hepatocellular carcinoma (HCC) 2, 3, 4, 5, 6
- Chronic hepatitis 2, 6
- Liver cirrhosis 2, 6
- Acute and chronic liver conditions 6
- Hereditary and other non-hepatic disorders 6
- ALT flare in chronic hepatitis B (CHB) 2
- Malignancies other than HCC, such as germ cell tumors and certain types of cancer 3
- Regeneration of liver cells after hepatic destruction 6
- Pregnancy, as AFP is produced by the fetus and can be detected in the mother's blood 3
- Infant and childhood conditions, such as neuroblastoma and certain congenital anomalies 3
Conditions Associated with Elevated AFP
Elevated AFP levels have been observed in various conditions, including:
- Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection 2
- Alcohol-related liver disease 2
- Obesity and diabetes 2
- Advanced liver disease 2
- Certain genetic disorders, such as ataxia-telangiectasia and Down syndrome 3
Limitations of AFP as a Tumor Marker
AFP has limitations as a tumor marker, including: