The AFP and AFP-L3 panel is a blood test that helps identify and monitor liver cancer, especially hepatocellular carcinoma (HCC), in people who are already at high risk due to conditions like cirrhosis or chronic hepatitis B or C. AFP, or alpha-fetoprotein, is a protein normally made by the fetus during pregnancy. In adults, it is usually present at very low levels. When AFP levels rise in a non-pregnant adult, it can signal abnormal liver activity, including liver cancer, but also non cancerous conditions such as viral hepatitis, alcoholic liver disease, or cirrhosis. This makes AFP a useful but imperfect tool—elevations are not always due to cancer, and many liver cancers, especially in early stages, don’t produce much AFP.
That’s where AFP-L3 comes in. AFP-L3 is a specific form of AFP that is made primarily by malignant liver cells. It binds to a sugar molecule called lens culinaris agglutinin, and this biochemical signature helps distinguish cancer-associated AFP from AFP elevated due to other causes. Measuring the percentage of AFP that is AFP-L3 (called AFP-L3%) can reveal whether a rise in AFP is more likely due to liver cancer or a benign process. An AFP-L3% above 10% is considered high and is associated with a significantly increased risk of developing HCC within 1 to 2 years. The test is especially useful in the diagnostic “gray zone,” when total AFP levels are elevated but not dramatically high—typically in the 20 to 200 ng/mL range. In these cases, a high AFP-L3% tips the balance toward a cancer diagnosis, and may prompt closer imaging follow-up or earlier treatment.
In patients undergoing treatment for HCC, this panel is also used to monitor the effectiveness of surgery, chemotherapy, or ablation. A falling AFP or AFP-L3 level usually means the treatment is working, while rising levels can signal tumor recurrence or spread. Importantly, neither marker alone is perfect. Some early liver cancers do not raise AFP or AFP-L3, and other tumors like germ cell cancers may also elevate AFP. That’s why doctors never rely on this panel alone—it’s always interpreted in the context of imaging and clinical findings. When used thoughtfully, though, this combination gives a more refined view of cancer risk and progression than either test on its own.
