From the Guidelines
Elevated alpha-fetoprotein (AFP) levels require immediate further investigation to determine the underlying cause, and patients should undergo additional testing including liver ultrasound, comprehensive liver function tests, and possibly CT or MRI imaging, as recommended by the most recent guidelines 1. When AFP is found to be high, it is essential to identify the underlying cause, as elevated levels in adults may indicate hepatocellular carcinoma, testicular cancer, or other malignancies. Non-cancerous causes include chronic hepatitis, cirrhosis, and pregnancy (as AFP is produced by the fetal liver). The normal range for adults is typically less than 10 ng/mL, with levels above this threshold warranting investigation. For pregnant women, AFP screening is part of routine prenatal care between 15-20 weeks gestation, where abnormal levels may indicate neural tube defects or chromosomal abnormalities. Management depends on identifying the underlying cause, with regular monitoring recommended for patients with chronic liver disease. The degree of elevation often correlates with disease severity, particularly in liver cancer where very high levels (>400 ng/mL) strongly suggest malignancy, as noted in previous studies 1. However, the most recent guidelines emphasize the importance of a multidisciplinary approach to managing hepatocellular carcinoma, including the use of liver ultrasonography and serum alpha-feto protein (AFP) for surveillance, as well as the consideration of newer imaging modalities and biomarkers 1. Key points to consider in the management of elevated AFP levels include:
- The use of liver ultrasonography as the recommended imaging tool for surveillance, with or without AFP level measurement 1
- The importance of identifying the underlying cause of elevated AFP levels, including hepatocellular carcinoma, testicular cancer, and non-cancerous causes such as chronic hepatitis and cirrhosis
- The role of CT or MRI imaging in characterizing liver nodules and diagnosing hepatocellular carcinoma, particularly in cases where ultrasound is inconclusive or unavailable 1
- The consideration of newer biomarkers and imaging modalities, such as des-gamma-carboxy prothrombin (DCP) and hepatobiliary MR contrast agents, in the diagnosis and management of hepatocellular carcinoma 1.
From the Research
Elevated Alpha-Fetoprotein Level
Elevated alpha-fetoprotein (AFP) levels can be indicative of various conditions, including hepatocellular carcinoma (HCC). The following points summarize the key findings related to elevated AFP levels:
- Elevated AFP levels are predictive of mortality after orthotopic liver transplant (OLT) for HCC, with higher AFP levels associated with poorer survival rates 2.
- A study of 386 patients with elevated AFP (>20 ng/ml) found that 78% of adults had some type of malignancy, predominantly HCC, while 73% of infants and children had elevated AFP without malignancy 3.
- AFP is an important biomarker for the diagnosis of HCC, and persistently increased AFP levels are a risk factor for HCC progression 4.
- The alpha-fetoprotein to transaminase ratio (AFP/(AST*ALT)) has been shown to have higher diagnostic efficacy for HCC compared to AFP alone, with an area under the receiver-operating curve (AUROC) of 0.853 5.
- The utility of AFP as a tumor marker for HCC is limited due to low sensitivity and specificity, and its accuracy varies according to patient characteristics and AFP cut-off values used 6.
- Combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73), and des-gamma-carboxyprothrombin can improve its accuracy in detecting HCC 6.
Possible Causes and Associations
Possible causes and associations of elevated AFP levels include:
- Hepatocellular carcinoma (HCC) 2, 3, 4, 5, 6
- Liver disease and cirrhosis 2, 3, 5
- Acute and chronic liver conditions 6
- Hereditary and non-hepatic disorders 6
- Malignancies other than HCC 3
Diagnostic and Prognostic Value
The diagnostic and prognostic value of elevated AFP levels is summarized as follows: