Alpha-Fetoprotein (AFP) is a protein produced in high amounts by the liver and yolk sac of a developing fetus. After birth, production significantly decreases, and it is found only in very low concentrations in the bloodstream of healthy adults. Elevated levels of AFP in an adult, particularly if sustained or rising, can indicate serious health issues. The most notable reason for a significant rise in AFP is hepatocellular carcinoma (HCC), the most common form of liver cancer.
Understanding AFP Measurement and Normalcy
Measuring Alpha-Fetoprotein is done through a simple blood test analyzed in a laboratory. The standard unit of measurement for AFP concentration is nanograms per milliliter (ng/mL). Establishing a baseline is important for interpreting results, as any level above this range is considered an elevation.
For healthy, non-pregnant adults, the normal reference range typically falls below 10 ng/mL, though some labs may use a cutoff up to 20 ng/mL. Normal AFP levels do not rule out cancer, as some individuals with liver tumors maintain levels within the healthy range.
Interpreting Elevated Levels in Hepatocellular Carcinoma
The interpretation of elevated AFP levels is linked to the probability and stage of Hepatocellular Carcinoma (HCC). Levels slightly above the normal threshold, such as between 20 ng/mL and 200 ng/mL, are often considered suspicious, especially in patients with underlying liver disease like cirrhosis. For these patients, an AFP value exceeding 200 ng/mL is a strong indicator of possible HCC.
Significantly higher AFP concentrations often correlate with larger tumor size and more advanced disease. Levels above 400 ng/mL are frequently associated with a liver tumor, and concentrations exceeding 500 ng/mL or 1,000 ng/mL are highly suggestive of aggressive or advanced HCC. The sensitivity of the AFP test increases substantially with tumor size.
AFP levels alone are rarely used to make a definitive diagnosis of liver cancer. Since not all HCC tumors produce AFP, and other conditions can cause mild elevations, imaging studies like ultrasound, CT, or MRI are always needed for confirmation. The combination of a rising AFP level and characteristic findings on imaging provides the most reliable evidence for an HCC diagnosis.
AFP’s Role in Treatment Monitoring and Recurrence
After a diagnosis of HCC is confirmed, sequential AFP testing is used to monitor how effectively the treatment is working. A significant and rapid drop in AFP levels following an intervention like surgical removal of the tumor or local ablation indicates a positive response. Ideally, successful treatment will cause the AFP level to fall back toward the normal range of below 10 ng/mL.
If the cancer is being treated with systemic therapy, a reduction in AFP levels by 50% or more is often considered a sign of a favorable response to the medication. Conversely, if the AFP level remains high or continues to rise after treatment, it suggests the cancer is not responding to therapy or that the disease is progressing. Monitoring AFP over time is also a standard practice for detecting the earliest signs of the cancer returning.
A sustained increase in AFP after a period of being low or normal is a strong suggestion of disease recurrence. This rise can sometimes be detected before the recurrent tumor is visible on imaging scans, making it a valuable tool for post-treatment surveillance. Patients who had high AFP levels before treatment and then experienced a decline, only to have them rise again, are often considered at a high risk for recurrence and poorer outcomes.
Factors That Complicate AFP Interpretation
The utility of the AFP test is limited because approximately one-third of HCC cases are AFP-negative. This means a normal AFP result does not guarantee the absence of liver cancer. This lack of sensitivity is why AFP is used in combination with liver imaging rather than as a standalone screening tool.
Several non-cancerous conditions can also cause an elevation in AFP, complicating interpretation. These benign causes include chronic liver conditions, such as cirrhosis and chronic hepatitis, or acute liver inflammation or injury. The elevated AFP is often modest in these cases, but it can complicate the differentiation between inflammation and malignancy.
Pregnancy is a common physiological cause of elevated AFP. Therefore, AFP results must always be interpreted in the full clinical context, considering the patient’s health status. The presence of non-cancerous causes means a high AFP level necessitates further diagnostic workup, such as specialized imaging, to determine the true cause.