What does an elevated Alpha-Fetoprotein (AFP) signify?

From the Guidelines

An elevated Alpha-Fetoprotein (AFP) level primarily signifies potential hepatocellular carcinoma (HCC), particularly in patients with chronic HBV and HCV, as well as other cancers such as intrahepatic cholangiocarcinoma, some metastases from colon cancer, lymphoma, and germ cell tumors 1. When interpreting an elevated AFP level, it is essential to consider the patient's context, including their age, sex, pregnancy status, and medical history.

• The degree of elevation is also crucial, as slight increases might indicate benign liver conditions, while dramatic elevations often suggest malignancy.
• Elevated AFP levels can also be seen in pregnancy, where abnormal levels may suggest neural tube defects, Down syndrome, or other fetal abnormalities.
• However, in the context of suspected HCC, an elevated AFP level in conjunction with imaging results showing a growing liver mass has been shown to have a high positive predictive value for HCC 1.
• It is also important to note that the diagnostic accuracy of an absolute AFP cutoff value has not been validated, and such values may vary by institution and patient population 1.
• Therefore, additional imaging studies, such as CT or MRI, are recommended for patients with a rising serum AFP level in the absence of a liver mass, and biopsy may be considered when a lesion is suspicious for malignancy 1.

From the Research

Elevated Alpha-Fetoprotein (AFP) Significance

Elevated Alpha-Fetoprotein (AFP) levels can signify various conditions, including:

• Malignancies, particularly hepatocellular carcinoma (HCC) and germ cell tumors (GCTs) 2, 3, 4, 5, 6
• Liver disease, such as cirrhosis, without HCC 2, 5, 6
• Other rare aggressive tumors, like AFP-producing gastric cancer (AFPGC) 4

Associated Factors

Several factors are associated with elevated AFP levels, including:

• Demographic characteristics: female gender 5, 6
• Clinical characteristics: presence of cirrhosis, liver disease with viral etiology, elevated alanine aminotransferase level, low albumin level, and vascular invasion 5
• Oncologic characteristics: HCC tumor size >2 cm, multinodular HCC, and advanced tumor stage 5, 6
• Viral etiology: HBV- or HCV-positive status 6

Clinical Implications

Elevated AFP levels can have significant clinical implications, including:

• Predictive of mortality after orthotopic liver transplant (OLT) for HCC 3
• Association with poor prognosis and survival outcomes in HCC patients 3, 5, 6
• Importance of thorough evaluation to rule out malignant disease in patients with elevated AFP levels 2