Frequency of elevated hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C

Abstract

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: ClinicalTrials.gov NCT00006164.

Figure 1. Frequency of DCP, AFP, and AFP-L3 elevations in 809 controls and 46 HCC cases during months 13 - 48

Figure 2

Figure 2a. ROC curves for maximum AFP and DCP between months 37 and 48 as predictors of HCC during months 37-60. The analysis includes 743 patients, 25 of whom developed HCC. The areas under the ROC curve are 0.76 for AFP and 0.70 for DCP. Figure 2b. ROC curves for maximum AFP and DCP between months 37 and 48 as predictors of HCC during months 37-60 for patients with cirrhosis at S00 or M24. The analysis includes 378 patients, 20 of whom developed HCC. . The areas under the ROC curve are 0.75 for AFP and 0.66 for DCP.

Figure 2

Figure 2a. ROC curves for maximum AFP and DCP between months 37 and 48 as predictors of HCC during months 37-60. The analysis includes 743 patients, 25 of whom developed HCC. The areas under the ROC curve are 0.76 for AFP and 0.70 for DCP. Figure 2b. ROC curves for maximum AFP and DCP between months 37 and 48 as predictors of HCC during months 37-60 for patients with cirrhosis at S00 or M24. The analysis includes 378 patients, 20 of whom developed HCC. . The areas under the ROC curve are 0.75 for AFP and 0.66 for DCP.