Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma
Background & Aims
The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. The aim of this study was to compare the accuracy of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in the early diagnosis of HCC.
Methods
Among 1031 patients randomized in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial, a nested case-control study of 39 HCC cases (24 early stage) and 77 matched controls was conducted to compare the performance of AFP and DCP. Testing was performed on sera from 12 months prior (month −12) to the time of HCC diagnosis (month 0).
Results
The sensitivity and specificity of DCP at month 0 was 74% and 86%, respectively, at a cutoff of 40 mAU/mL and 43% and 100%, respectively, at a cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61% and 81% at a cutoff of 20 ng/mL and 22% and 100% at a cutoff of 200 ng/mL. At month −12, the sensitivity and specificity at the low cutoff was 43% and 94%, respectively, for DCP and 47% and 75%, respectively, for AFP. Combining both markers increased the sensitivity to 91% at month 0 and 73% at month 12, but the specificity decreased to 74% and 71%, respectively. Diagnosis of early HCC was triggered by surveillance ultrasound in 14, doubling of AFP in 5, and combination of tests in 5 patients.
Conclusions
Biomarkers are needed to complement ultrasound in the detection of early HCC, but neither DCP nor AFP is optimal.
Abbreviations used in this paper: AFP, α-fetoprotein, AUROC, area under receiver operating characteristic curve, CT, computed tomography, DCP, des-γ-carboxy prothrombin, HALT-C, Hepatitis C Antiviral Long-term Treatment Against Cirrhosis, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, MRI, magnetic resonance imaging
Conflicts of interest The authors disclose the following:Financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: A.S. Lok is a consultant; R.K. Sterling is a consultant, receives research support, and is on the speaker's bureau; J.C. Hoefs is on the speaker's bureau; T.R. Morgan is a consultant, on the speaker's bureau, and receives research support; A.M. Di Bisceglie is a consultant, on the speaker's bureau, and receives research support; W.M. Lee receives research support; and H.L. Bonkovsky receives research support. Financial relationships of the authors with Eisai Co, Ltd, are as follows: A.S. Lok receives research support. The remaining authors disclose no conflicts.
Funding Supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below); the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute; the National Center for Minority Health and Health Disparities; by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources and National Institutes of Health (grant numbers are listed below); by Eisai Co, Ltd, through a Materials Cooperative Research and Development Agreement (M-CRADA) with the National Institutes of Health for testing of des-γ-carboxy prothrombin; and by Hoffmann–La Roche, Inc, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.
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PII: S0016-5085(09)01857-5
doi:10.1053/j.gastro.2009.10.031
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
