Gastroenterology

Gastroenterology

Volume 138, Issue 2, February 2010, Pages 493-502
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma

https://doi.org/10.1053/j.gastro.2009.10.031Get rights and content

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.

Section snippets

HALT-C Trial Design, HCC Definition, and Surveillance

The design of the HALT-C Trial has been described previously.27, 28 All patients were required to have an ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) with no evidence of hepatic mass lesions suspicious for HCC and a serum AFP <200 ng/mL prior to enrollment (except for 3 patients who had AFP values of 206, 212, and 315 ng/mL). Liver biopsy specimens were reviewed in conference by a panel of 12 hepatic pathologists, who used the Ishak scoring system to stage fibrosis

Baseline AFP and DCP Values of All Randomized Patients

Of the 1050 patients randomized, baseline AFP and/or DCP values were not available in 19. Thus, 1031 (98.2%) patients were included in this analysis. Baseline characteristics of these patients (39 HCC cases, 77 matched controls, and 915 other non-HCC patients) are shown in Table 1. The mean age of these 1031 patients was 50 years, 29% were women, and 18% were black. Cirrhosis was present on baseline biopsy specimens in 41% of patients. Half (49%) of the patients were randomized to maintenance

Discussion

This analysis took advantage of the large cohort of at-risk patients followed prospectively in the HALT-C Trial to compare the accuracy of AFP and DCP in the early detection of HCC and to determine factors that might affect the performance of these markers. The availability of samples before the diagnosis of HCC allowed for the comparison of the accuracy of AFP and DCP in differentiating HCC cases from matched controls before clinical diagnosis, an important feature in HCC surveillance. DCP had

Acknowledgments

This is publication No. 45 from the HALT-C Trial Group.

The HALT-C Trial is registered with clinicaltrials.gov (No. NCT00006164).

H.L.B.'s current address is Carolinas Medical Center, Charlotte, North Carolina.

In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct, and/or care of patients enrolled in this study at each of the participating institutions as follows:

University of Massachusetts Medical Center, Worcester, MA: (contract

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    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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