The SAGE IVD recommended full listing of alpha fetoprotein (AFP) test for the purpose of liver disease. Recommended test purpose: screening for hepatocellular carcinoma (HCC) in high-risk individuals with chronic hepatitis B or C, cirrhosis, or a family history of HCC, in conjunction with ultrasound and for staging and disease monitoring of germ-cell tumours. The SAGE IVD recommended conditional inclusion on the EDL of AFP testing, pending submission of further evidence to support recommendations in international guidelines on its use in the staging, determining the intensity of treatment and monitoring of germ-cell tumours, especially in adolescents. The Group called for a systematic review of thresholds for AFP that indicate the presence of malignancy. In 2020 WHO proposed adding "diagnosis and staging of hepatoblastoma” to the test purpose. The working group accepted the rationale provided and agreed that the test should be used to aid in the diagnosis of hepatoblastoma and staging of hepatoblastoma. Therefore, “to aid in the diagnosis and staging of hepatoblastoma” was added to the test purpose of AFP. Detailed information available here: https://iris.who.int/handle/10665/339064

The test is recommended for screening people at high risk for hepatocellular carcinoma (HCC) (with chronic hepatitis B or C, cirrhosis, or a family history of HCC), in conjunction with ultrasound, consistent with WHO guidelines, although testing by ultrasound should have precedence over alpha fetoprotein (AFP) testing. The test is also used for staging and disease monitoring of germ-cell tumours for deciding the intensity of treatment, although there are few data on this use. Consensus documents on staging and management of adolescent tumours include AFP, as ultrasound is not sufficient for paediatric tumours, and testing for AFP and hCG are necessary. The advantage of AFP testing is that it is done on blood samples, which can be sent elsewhere, whereas ultrasound requires the person to be present. Expert opinion and systematic reviews on AFP thresholds should be provided. In 2020 WHO proposed adding "diagnosis and staging of hepatoblastoma” to the test purpose. The working group accepted the rationale provided and agreed that the test should be used to aid in the diagnosis of hepatoblastoma and staging of hepatoblastoma. Therefore, “to aid in the diagnosis and staging of hepatoblastoma” was added to the test purpose of AFP. Detailed information available here: https://iris.who.int/handle/10665/339064

Monitoring patients at high risk of hepatocellular carcinoma (HCC) with alpha fetoprotein (AFP) combined with ultrasound is effective in detecting HCC (WHO guidelines). AFP testing is recommended by WHO for screening for HCC in patients with cirrhosis in the guidelines for the management of viral hepatitis B and C, including monitoring high- risk patients. Use of AFP increased the sensitivity of detection of early HCC in patients with cirrhosis in a metanalysis (RR 0.81; 95% CI 0.71 ; 0.93), with a sensitivity of 63% (95% CI: 48 ; 75), demonstrating its effectiveness for detecting more diseases at an earlier stage, when it is eligible for curative treatment (4). AFP has also been suggested as a prognostic marker for HCC, with an HR for survival of 4.35 when AFP is > 1000 ng/mL (11). AFP testing is recognized as an aid in diagnosis, prognosis, staging and disease monitoring for germ-cell tumours in international guidelines (6–8). AFP testing plays a critical role in prognostication of germ-cell tumours, in risk classification of advanced tumours and in risk- adapted intensity of treatments for patients, according to the International Germ Cell Cancer Collaborative Group (8), as well as in early monitoring of the response of non-seminomatous germ-cell tumours, to anticipate platinum resistance and intensify treatment in a personalized approach (10).

World Health Organization. (‎2019)‎. The selection and use of essential in vitro diagnostics: report of the second meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics (‎including the second WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/329527 ; World Health Organization. (‎2021)‎. The selection and use of essential in vitro diagnostics: report of the third meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2020 (‎including the third WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/339064