Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma

Anna S. Lok, Richard K. Sterling, James E. Everhart, Elizabeth C. Wright, John C. Hoefs, Adrian M. Di Bisceglie, Timothy R. Morgan, Hae Young Kim, William M. Lee, Herbert L. Bonkovsky, Jules L. Dienstag

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)493-502
Number of pages10
JournalGastroenterology
Volume138
Issue number2
DOIs
StatePublished - Feb 2010

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Fetal Proteins
Prothrombin
Hepatocellular Carcinoma
Biomarkers
Sensitivity and Specificity
Delayed Diagnosis
Hepatitis C
Antiviral Agents
Case-Control Studies
Early Diagnosis
Fibrosis
Serum

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lok, A. S., Sterling, R. K., Everhart, J. E., Wright, E. C., Hoefs, J. C., Di Bisceglie, A. M., ... Dienstag, J. L. (2010). Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma. Gastroenterology, 138(2), 493-502. https://doi.org/10.1053/j.gastro.2009.10.031

Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma. / Lok, Anna S.; Sterling, Richard K.; Everhart, James E.; Wright, Elizabeth C.; Hoefs, John C.; Di Bisceglie, Adrian M.; Morgan, Timothy R.; Kim, Hae Young; Lee, William M.; Bonkovsky, Herbert L.; Dienstag, Jules L.

In: Gastroenterology, Vol. 138, No. 2, 02.2010, p. 493-502.

Research output: Contribution to journalArticle

Lok, AS, Sterling, RK, Everhart, JE, Wright, EC, Hoefs, JC, Di Bisceglie, AM, Morgan, TR, Kim, HY, Lee, WM, Bonkovsky, HL & Dienstag, JL 2010, 'Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma', Gastroenterology, vol. 138, no. 2, pp. 493-502. https://doi.org/10.1053/j.gastro.2009.10.031
Lok, Anna S. ; Sterling, Richard K. ; Everhart, James E. ; Wright, Elizabeth C. ; Hoefs, John C. ; Di Bisceglie, Adrian M. ; Morgan, Timothy R. ; Kim, Hae Young ; Lee, William M. ; Bonkovsky, Herbert L. ; Dienstag, Jules L. / Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma. In: Gastroenterology. 2010 ; Vol. 138, No. 2. pp. 493-502.
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abstract = "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.",
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AU - Everhart, James E.

AU - Wright, Elizabeth C.

AU - Hoefs, John C.

AU - Di Bisceglie, Adrian M.

AU - Morgan, Timothy R.

AU - Kim, Hae Young

AU - Lee, William M.

AU - Bonkovsky, Herbert L.

AU - Dienstag, Jules L.

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N2 - 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.

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