From the Guidelines
Elevated alpha-fetoprotein (AFP) levels in nonpregnant individuals warrant further investigation, as they may indicate serious underlying conditions, with hepatocellular carcinoma (HCC) being a primary concern, and a thorough evaluation, including liver imaging and comprehensive liver function tests, is necessary to determine the cause of elevated AFP levels. In nonpregnant individuals, AFP levels are typically very low, and elevated levels (above 10 ng/mL) may suggest various conditions, including HCC, cirrhosis, hepatitis, and certain germ cell tumors 1. The degree of AFP elevation often correlates with disease severity, and very high levels (>500 ng/mL) strongly suggest malignancy 1. Regular monitoring of AFP levels can help track treatment response in patients with AFP-producing tumors. When evaluating elevated AFP levels, it is essential to consider the patient's risk factors, such as hepatitis B or C infection, alcoholic cirrhosis, and nonalcoholic fatty liver disease (NAFLD), as these conditions increase the risk of developing HCC 1. Some guidelines recommend using ultrasound (US) with or without AFP for HCC surveillance, while others consider AFP to be optional due to its limited sensitivity and specificity as a screening biomarker 1. However, AFP can still be useful in conjunction with other test results to guide the management of patients with suspected HCC, particularly in those with cirrhosis or other risk factors 1. Key points to consider when evaluating elevated AFP levels in nonpregnant individuals include:
- Elevated AFP levels warrant further investigation to determine the underlying cause
- HCC is a primary concern in nonpregnant individuals with elevated AFP levels
- A thorough evaluation, including liver imaging and comprehensive liver function tests, is necessary to determine the cause of elevated AFP levels
- Regular monitoring of AFP levels can help track treatment response in patients with AFP-producing tumors
- Patient risk factors, such as hepatitis B or C infection and NAFLD, should be considered when evaluating elevated AFP levels.
From the Research
Alpha Fetoprotein in Nonpregnant Persons
- Alpha fetoprotein (AFP) is a fetal-specific glycoprotein that falls rapidly after birth 2
- High levels of AFP in nonpregnant persons can be suspicious of hepatocellular carcinoma (HCC), but may also be elevated in chronic viral hepatitis 2
- A study found that a 35-year-old with chronic hepatitis B infection had high AFP levels (740.9 ng/ml) without evidence of HCC, which reduced with antiviral therapy 2
- Elevated AFP levels in asymptomatic individuals may play a role in expressing a protective phenotype against hepatic steatosis, myosteatosis, and sarcopenia 3
- A study investigated the clinical characteristics, outcomes, and relationship with body fat deposition and muscle mass in asymptomatic adults with elevated AFP levels (>7 ng/mL) 3
Diagnosis of Hepatocellular Carcinoma
- Abdominal ultrasound (US) and serum alpha-fetoprotein (AFP) measurement are used to diagnose HCC, but further testing is required to confirm diagnosis and staging 4
- A systematic review and meta-analysis found that the combination of AFP and US showed the highest sensitivity and less than 5% of HCC occurrences would be missed with about 15% of false-positive results 4
- The optimal threshold of AFP for diagnosing HCC is controversial, but a study found that a threshold of 400 ng/mL was better than 200 ng/mL in terms of sensitivity and specificity 5
Biology and Significance of Alpha-Fetoprotein
- AFP remains the most widely used and accepted serum marker for HCC despite the discovery of other biomarkers 6
- The regulation of AFP at the gene and protein levels, its pathophysiology as a pro-proliferative protein, and its correlation with molecular HCC subclasses are not fully understood 6
- AFP has historical and current uses for screening and surveillance, diagnosis, and as a prognostic and predictive biomarker in HCC 6