Validation of a novel model for the early detection of hepatocellular carcinoma

Philip M. Hemken, Lori J. Sokoll, Xiaoqing Yang, Jianliang Dai, Debra Elliott, Susan H. Gawel, Michael Lucht, Ziding Feng, Jorge A. Marrero, Sudhir Srivastava, Daniel W. Chan, Gerard J. Davis

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5 Scopus citations

Abstract

Background: The biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist-II (PIVKA-II) may be useful for detecting early-stage hepatocellular carcinoma (HCC). We evaluated the performance of AFP and PIVKA-II levels, alone and in combination with clinical factors, for the early detection of HCC. Methods: In a case-control study, serum AFP and PIVKA-II were measured using the ARCHITECT immunoassay analyzer system in a cohort of 119 patients with HCC, 215 patients with non-malignant liver disease, and 34 healthy subjects. Five predictive models for detecting HCC were developed based on age, gender, AFP, and/or PIVKA-II levels; the best model was validated in an independent cohort of 416 patients with HCC and 412 control subjects with cirrhosis. Results: In both cohorts, AFP and PIVKA-II concentrations were higher in patients with HCC compared to healthy controls and patients with non-malignant liver disease. The model that combined AFP and PIVKA-II, age, and gender had the highest AUC of 0.95 (0.95, 95% CI 0.93-0.98), with a sensitivity of 93% and a specificity of 84% in the development cohort, and an AUC of 0.87 (95% CI 0.85-0.90), sensitivity of 74%, and specificity of 85% in the validation cohort. When limiting the validation cohort to only early-stage HCC, the AUC was 0.85 (95% CI 0.81-0.88), sensitivity was 70%, and specificity was 86%. Conclusions: Compared to each biomarker alone, the combination of AFP and PIVKA-II with age and gender improved the accuracy of detecting HCC and differentiating HCC from non-malignant liver disease.

Original languageEnglish (US)
Article number2
JournalClinical Proteomics
Volume16
Issue number1
DOIs
StatePublished - Jan 16 2019

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Keywords

  • Biomarker
  • Cancer
  • Des-gamma carboxyprothrombin
  • Early diagnosis
  • Liver

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Hemken, P. M., Sokoll, L. J., Yang, X., Dai, J., Elliott, D., Gawel, S. H., Lucht, M., Feng, Z., Marrero, J. A., Srivastava, S., Chan, D. W., & Davis, G. J. (2019). Validation of a novel model for the early detection of hepatocellular carcinoma. Clinical Proteomics, 16(1), [2]. https://doi.org/10.1186/s12014-018-9222-0