From the Guidelines
Elevated Alpha-Fetoprotein (AFP) is a protein normally produced by the fetal liver that can be elevated in certain medical conditions, including liver cancer, testicular or ovarian germ cell tumors, and certain gastrointestinal cancers, as well as non-cancerous liver conditions such as cirrhosis, hepatitis, or liver damage. The most common causes of elevated AFP include hepatocellular carcinoma (HCC), which is a type of liver cancer, as well as other cancers such as testicular or ovarian germ cell tumors, and certain gastrointestinal cancers 1. During pregnancy, elevated maternal AFP can suggest neural tube defects in the developing fetus, multiple pregnancies, or certain chromosomal abnormalities like Down syndrome.
The significance of elevated AFP depends on the context and degree of elevation, with very high levels more strongly associated with cancer 1. For example, an elevated AFP level in conjunction with imaging results showing the presence of a growing liver mass has been shown to have a high positive predictive value for HCC in certain patient populations 1. However, the diagnostic accuracy of an absolute AFP cutoff value has not been validated in this setting, and such values may vary by institution and patient population.
Some of the key points to consider when evaluating elevated AFP include:
- Elevated AFP can be associated with a range of medical conditions, including liver cancer, testicular or ovarian germ cell tumors, and certain gastrointestinal cancers
- Non-cancerous liver conditions such as cirrhosis, hepatitis, or liver damage can also cause AFP elevation
- The significance of elevated AFP depends on the context and degree of elevation, with very high levels more strongly associated with cancer
- Further diagnostic testing is typically recommended if elevated AFP is detected, which may include imaging studies like ultrasound, CT scan, or MRI, and possibly tissue biopsy to determine the underlying cause 1. In clinical practice, it is essential to interpret AFP results in the context of other diagnostic tests and clinical findings, rather than relying solely on AFP levels to diagnose or rule out specific conditions.
From the Research
Definition of Elevated Alpha-Fetoprotein (AFP)
Elevated Alpha-Fetoprotein (AFP) refers to higher than normal levels of AFP in the blood. AFP is a glycoprotein secreted by the embryonic liver and is expressed in tumors with high mitotic index, such as hepatocellular carcinoma (HCC) and germ cell tumors 2, 3, 4.
Causes of Elevated AFP
The causes of elevated AFP include:
- Underlying HCC or germ cell tumor 2, 4
- Chronic viral hepatitis, particularly with active replication 2
- Hereditary persistence of AFP (HPAFP), a rare and benign condition with an autosomal dominant pattern of inheritance 2, 3, 4
- Other non-hepatic disorders 5
- Primary breast carcinoma in postmenopausal women 6
Hereditary Persistence of AFP (HPAFP)
HPAFP is a rare and benign condition characterized by persistently elevated AFP levels in the absence of underlying malignant processes. It is inherited in an autosomal dominant manner and can be confirmed by analyzing AFP levels in family members 3, 4. HPAFP should be suspected in patients with high AFP levels and no radiological evidence of HCC or germ cell tumor 2, 4.
Clinical Significance of Elevated AFP
Elevated AFP levels can signify the severity of hepatic destruction and subsequent regeneration, and are commonly observed in patients with acute and chronic liver conditions and cirrhosis 5. However, the utility of AFP as a tumor marker is limited due to its low sensitivity and specificity, and discrepancies among different methods of measurement 5.