title: The GALAD scoring algorithm based on AFP, AFP-L3, and DCP significantly improves detection of BCLC early stage hepatocellular carcinoma.
abstract: Background:Hepatocellular carcinoma (HCC) is one of the leading causes of death in cirrhotic patients worldwide. The detection rate for early stage HCC remains low despite screening programs. Thus, the majority of HCC cases are detected at advanced tumor stages with limited treatment options. To facilitate earlier diagnosis, this study aims to validate the added benefit of the combination of AFP, the novel biomarkers AFP-L3, DCP, and an associated novel diagnostic algorithm called GALAD.Material and methods:Between 2007 and 2008 and from 2010 to 2012, 285 patients newly diagnosed with HCC and 402 control patients suffering from chronic liver disease were enrolled. AFP, AFP-L3, and DCP were measured using the µTASWako i30 automated immunoanalyzer. The diagnostic performance of biomarkers was measured as single parameters and in a logistic regression model. Furthermore, a diagnostic algorithm (GALAD) based on gender, age, and the biomarkers mentioned above was validated.Results:AFP, AFP-L3, and DCP showed comparable sensitivities and specifities for HCC detection. The combination of all biomarkers had the highest sensitivity with decreased specificity. In contrast, utilization of the biomarker-based GALAD score resulted in a superior specificity of 93.3 % and sensitivity of 85.6 %. In the scenario of BCLC 0/A stage HCC, the GALAD algorithm provided the highest overall AUROC with 0.9242, which was superior to any other marker combination.Conclusions:We could demonstrate in our cohort the superior detection of early stage HCC with the combined use of the respective biomarkers and in particular GALAD even in AFP-negative tumors.
authors.affiliation: Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Best
authors.affiliation: Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bilgi
authors.affiliation: Straubing Center of Science, Department of Bioinformatics, Straubing, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Heider
authors.affiliation: Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schotten
authors.affiliation: Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Manka
authors.affiliation: Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bedreli
authors.affiliation: Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gorray
authors.affiliation: Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ertle
authors.affiliation: Vrije Universiteit Brussel (VUB Jette), Liver Cell Biology Laboratory, Brussels, Belgium.
authors.forename: L A
authors.initials: LA
authors.lastname: van Grunsven
authors.affiliation: Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie, Essen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dechêne
mesh_terms: D017677:Age Distribution; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C097353:AFP protein, human; D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin