Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients With Advanced Hepatitis C

Am J Gastroenterol. 2012 Jan;107(1):64-74. doi: 10.1038/ajg.2011.312. Epub 2011 Sep 20.


Objectives: Prospective studies of serum hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C are lacking. The aim of this study was to determine the frequencies and performance of elevated α-fetoprotein (AFP), AFP-L3, and des-γ-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C.

Methods: Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop.

Results: In all, 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20 and 199, and 2.3% had at least one AFP value ≥200 ng/ml; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90 and 149, and 14.7% had at least one DCP value ≥150 mAU/ml. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP ≥20 ng/ml. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/ml had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/ml had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC.

Conclusions: Mild-moderate elevations in total AFP and DCP but not in AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC.

Trial registration: NCT00006164.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Biomarkers / blood*
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / complications*
  • Disease Progression
  • Female
  • Hepatitis C / complications*
  • Humans
  • Liver Neoplasms / blood*
  • Liver Neoplasms / complications*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Protein Isoforms / blood
  • Protein Precursors / blood*
  • Prothrombin
  • alpha-Fetoproteins / analysis*


  • Biomarkers
  • Protein Isoforms
  • Protein Precursors
  • alpha-Fetoproteins
  • acarboxyprothrombin
  • Prothrombin

Associated data