Alpha-fetoprotein, Des-gamma Carboxyprothrombin, and Lectin-Bound Alpha-fetoprotein in Early Hepatocellular Carcinoma

By Jorge A. Marrero, Ziding Feng, Yinghui Wang, Mindie H. Nguyen, A. Befeler, Lewis R. Roberts, K. Reddy, D. Harnois, J. Llovet, D. Normolle and 6 more. Gastroenterology, 2009

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Background and Aims Alpha-fetoprotein (AFP) is widely used as a surveillance test for Hepatocellular carcinoma (HCC) among patients with cirrhosis. Des-gamma carboxy-prothrombin (DCP) and lectin-bound AFP (AFP-L3) are potential surveillance tests for HCC. The aims of this study were to determine performance of DCP and AFP-L3 for the diagnosis of early HCC, whether they complement AFP, and what factors affect DCP, AFP-L3 or AFP levels. Methods We conducted a large phase 2 biomarker case-control study in 7 academic medical centers in the United States. Controls were patients with compensated cirrhosis and cases were patients with HCC. AFP, DCP and AFP-L3 levels were measured blinded to clinical data in a central reference laboratory. Results A total of 836 patients were enrolled, 417 (50%) were cirrhosis controls and 419 (50%) were HCC cases, of which 208 (49.6%) had early stage HCC (n=77 very early, n=131 early). AFP had the best area under the ROC curve (0.80, 95%CI: 0.77–0.84) followed by DCP (0.72, 95%CI: 0.68–0.77) and AFP-L3% (0.66, 95%CI: 0.62–0.70) for early stage HCC. The optimal AFP cutoff value was 10.9 ng/ml leading to a sensitivity of 66%. When only those with very early HCC were evaluated, the AUC for AFP was 0.78 (95%CI: 0.72–0.85) leading to a sensitivity of 65% at the same cutoff. Conclusion AFP was more sensitive than DCP and AFP-L3 for the diagnosis of early and very early stage HCC at a new cutoff of 10.9 ng/mL.

Subfields: Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/f584d70683a9111e884acf56873e73ab81108bfe

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Citations in the corpus

Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases (2019, background): “The differential diagnosis includes both benign and malignant entities, such as, respectively, vascular pseudolesions (usually attributed to arterioportal shunts) and small HCCs.”
Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases (2018, background): “The differential diagnosis includes both benign and malignant entities, such as, respectively, vascular pseudolesions (usually attributed to arterioportal shunts) and small HCCs.”
Management of hepatocellular carcinoma: An update (2011, critical): “Another recent study that suggested that AFP is a good surveillance test suffers from methodological flaws.(135) Among others, it was not really a surveillance study, but one in which the presence of HCC was known (i.”
AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma (2023, neutral): “…vitamin K absence/antagonist-II (PIVKA-II), a variant of prothrombin that is also specifically produced at high levels by a proportion of HCCs. [76,77] These biomarkers are currently Food and Drug Administration (FDA) approved for risk stratification but not HCC surveillance in the United States.”