Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma

Gastroenterology. 2010 Feb;138(2):493-502. doi: 10.1053/j.gastro.2009.10.031. Epub 2009 Oct 20.

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 alpha-fetoprotein (AFP) and des-gamma-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.

Trial registration: ClinicalTrials.gov NCT00006164.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Case-Control Studies
  • Female
  • Humans
  • Liver / diagnostic imaging
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / diagnostic imaging
  • Male
  • Middle Aged
  • Protein Precursors / blood*
  • Prothrombin
  • Randomized Controlled Trials as Topic
  • Sensitivity and Specificity
  • Ultrasonography
  • alpha-Fetoproteins / metabolism*

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Protein Precursors
  • alpha-Fetoproteins
  • acarboxyprothrombin
  • Prothrombin

Associated data

  • ClinicalTrials.gov/NCT00006164

Grant support