AFP is a glycoprotein homologous to albumin. Normally produced during gestation by the fetal liver,

Malignancies with elevated levels:
Mainly confined to three malignancies, ie

1. Hepatocellular carcinoma - elevated in 70 - 90% cases
2. Non-seminomatous germ cell tumours of testis, ovary and other sites - elevated in 40 - 60% of patients with testicular germ cell tumours. Rarely elevated in patients with stage one testicular cancer.
3. Hepatoblastoma (in children, extremely rare in adults)

Physiological causes for raised AFP:
AFP is high in newborns with levels declining to adult values by one year of age. AFP is also elevated in pregnancy.

Benign conditions which may have elevated levels:
Hepatitis, cirrhosis, biliary tract obstruction, alcoholic liver disease and ataxia telangiectasia. 20-40% of adult patients with hepatitis or cirrhosis have raised AFP levels and AFP concentrations up to 1000 µg/l may occur in benign conditions. AFP concentrations >50µg/L should be referred for specialist hepatobiliary interpretation.

Main clinical applications:

In general, AFP should only be requested in patients with established cirrhosis or in whom a hepatic lesion has been demonstrated by imaging

1. Diagnostic aid for hepatocellular carcinoma. An AFP concentration between 400 - 500 µg/l is now generally accepted as the optimal decision point to distinguish hepatocellular carcinoma from chronic liver disease. In general, a sustained rise in AFP is suggestive of malignancy, while stable or decreasing results make it less likely. A rising concentration over a period of time is more significant than the absolute concentration e.g. a doubling from 10µg/L to 20µg/L and then a rise to 50µg/L is much more suggestive of malignancy than a single value of 80µg/L.
2. Screening for hepatocellular carcinoma in high risk disease groups eg haemochromatosis, alcoholic cirrhosis (if abstinent) cirrhosis due to hepatitis C hepatitis B surface antigen positive carriers with chronic active hepatitis / cirrhosis males with primary biliary cirrhosis) Small hepatocellular tumours are AFP negative in up to 40% cases. In these instances, the tumour can only be detected by ultrasound. Lesions undetectable by imaging are likely to reach 2cm in diameter in about 4 -12 months, so in order to detect tumours below 2cm, the suggested interval for surveillance in cirrhotic patients is 6 months, using both serum AFP and ultrasound.
3. In combination with HCG, for monitoring patients with non-seminomatous germ cell tumours.
4. Independent prognostic marker for non-seminomatous germ cell tumours
5. Diagnosis of hepatoblastoma

AFP: new reference interval 01/05/21.
RLH service users: results unaffected.
AUH service users: AFP now reported in ug/L, values 20 % higher than previously.

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