AFP
Alpha-Fetoprotein
What it is
Alpha-fetoprotein (AFP) is a glycoprotein produced at high levels by the fetal liver, yolk sac, and gastrointestinal tract during fetal development. AFP is the fetal analogue of albumin — the major protein in fetal serum — and its production is largely silenced after birth, falling to very low levels (typically < 10 ng/mL) in healthy adults. Re-expression of AFP in elevated concentrations in adults occurs in three main contexts: hepatocellular carcinoma (HCC, the most common primary liver cancer), in which AFP is elevated in approximately 60–80% of cases; non-seminomatous germ cell tumours (NSGCTs) — testicular and ovarian yolk sac tumours and mixed teratomas — in which AFP is markedly elevated and used both for diagnosis and treatment monitoring; and, at lower levels, in active liver disease (cirrhosis, hepatitis) reflecting hepatocyte regeneration and damage rather than malignancy. AFP is also used in maternal serum screening during pregnancy (elevated AFP can indicate neural tube defects; low AFP can indicate chromosomal abnormalities) — a completely different clinical context from its oncological use in adults.
Why we measure it
Hepatocellular carcinoma is the most common primary liver cancer and the third most common cause of cancer death worldwide. Its prognosis is dramatically stage-dependent: five-year survival for localised HCC is approximately 30%, falling to under 3% for metastatic disease. The major risk factors — chronic hepatitis B and C infection, cirrhosis of any cause, metabolic-associated fatty liver disease (MAFLD) with significant fibrosis, and aflatoxin exposure — are identifiable from the rest of the Blueprint protocol. AFP surveillance (typically every 6 months alongside liver ultrasound for high-risk individuals) is recommended by international liver societies for those with cirrhosis and chronic hepatitis B. In a broader health screening context, annual AFP provides a baseline for individuals whose protocol may reveal risk factors for HCC — elevated liver enzymes, metabolic syndrome, or relevant serological findings — and detects the rising AFP trend that can precede clinical symptoms by months. A sustained or rising AFP, even within the 'normal' range, in an individual with known liver disease warrants liver imaging. For younger males, an elevated AFP combined with a testicular or abdominal mass is a near-diagnostic combination for NSGCT.
Why every 12 months
Annual AFP is appropriate for population-level surveillance in individuals without known liver disease or identified risk factors. In individuals with cirrhosis, chronic hepatitis B, or other established HCC risk factors, more frequent monitoring (every 6 months) alongside liver ultrasound is recommended by hepatology societies. The annual draw provides the baseline and trend data that contextualise any future elevation.
What movement means
The standard upper reference limit for AFP in adults is 10 ng/mL, though some laboratories use 7 or 8 ng/mL. Levels between 10 and 20 ng/mL are a 'grey zone' with overlap between active liver disease and early HCC. Levels above 400–500 ng/mL in an individual with a liver mass are strongly associated with HCC. Testicular NSGCT typically produces AFP in the hundreds to thousands of ng/mL range.
Normal
< 10 ng/mL
Within the standard reference range for healthy adults. Trend across annual draws is informative — a stable value below 5 ng/mL is reassuring. Any sustained rise within or approaching the upper reference limit warrants monitoring, particularly in individuals with metabolic liver disease or known hepatitis.
Standard laboratory reference ranges — vary by assay method
Borderline
10 – 20 ng/mL
Mild elevation. May reflect active liver disease (hepatitis, cirrhosis) rather than malignancy. Liver function tests, viral hepatitis serology, and repeat AFP should be assessed. In the presence of a liver mass on imaging, even borderline AFP is diagnostically significant.
Bruix J, Sherman M, American Association for the Study of Liver Diseases, Hepatology, 2011
Elevated
> 20 ng/mL
Warrants liver imaging (ultrasound or CT/MRI) and hepatology review. In an individual without known liver disease, elevated AFP combined with abnormal liver enzymes suggests occult liver pathology. AFP > 400 ng/mL in the presence of a liver mass is considered near-diagnostic for HCC by international liver society criteria.
European Association for the Study of the Liver (EASL) HCC Clinical Practice Guidelines, Journal of Hepatology, 2018
In the protocol
References
- 1.
Bruix J, Sherman M; American Association for the Study of Liver Diseases. “Management of Hepatocellular Carcinoma: An Update.” Hepatology. 2011.
- 2.
European Association for the Study of the Liver. “EASL Clinical Practice Guidelines: Management of Hepatocellular Carcinoma.” Journal of Hepatology. 2018.
- 3.
Deugnier Y, Turlin B. “Pathology of Hepatic Iron Overload.” World Journal of Gastroenterology. 2007.
- 4.
International Germ Cell Cancer Collaborative Group. “International Germ Cell Consensus Classification: A Prognostic Factor-Based Staging System for Metastatic Germ Cell Cancers.” Journal of Clinical Oncology. 1997.