A Combination of α-Fetoprotein and Des-γ-Carboxy Prothrombin Is Superior in Detection of Hepatocellular Carcinoma

Abstract

Background and Aim: The incidence of hepatocellular carcinoma (HCC) is increasing in western countries. Despite its low sensitivity, the diagnosis of HCC still depends on detection of α-fetoprotein (AFP). Therefore, the aim of this study was to evaluate the combined analysis of AFP and des-γ-carboxy prothrombin (DCP) in a European cohort. Methods: We performed a single-center study (164 HCC/422 controls), in which the serum concentrations of AFP and DCP were determined. Results: AFP and DCP were elevated in HCC patients compared to controls (p < 0.0001). By combination of AFP and DCP, the sensitivity was improved from 28.7% for AFP (cutoff 400 ng/ml; AFP at cutoff 10 ng/ml: 54.9%) to 78.0% using cutoffs of 10 ng/ml for AFP and 5 ng/ml for DCP (DCP alone, cutoff 5 ng/ml: 63.4%). Among early-stage patients, the sensitivity increased from 20% for AFP (cutoff 400 ng/ml; AFP at cutoff 10 ng/ml: 38%) to 55% in combination (DCP alone, cutoff 5 ng/ml: 47%). The area under the curve (AUC) for AFP and DCP was similar (AFP: 0.88; DCP: 0.87; combined: 0.91). Among non-cirrhotic patients, DCP (AUC: 0.93) showed a better performance than AFP (AUC: 0.84). Especially patients with non-alcoholic steatohepatitis had a high percentage of DCP-positive tumors. Conclusion: The data suggest that AFP alone is not sufficient for the serological diagnosis of HCC in European patients, while a combination of AFP and DCP can increase the sensitivity even in early-stage patients.

Diagnostic Accuracy of PIVKA-II, Alpha-Fetoprotein and a Combination of both in Diagnosis of Hepatocellular Carcinoma in Patients Affected by Chronic HCV Infection

“…It is synthesized in the presence of acquired defects of precursor carboxylation found in patients with HCC (5,10). PIVKA-II may have a role in HCC progression by acting as an autologous growth factor (11)(12)(13).…”

“…For these reasons, some authors, and especially Japanese guidelines on HCC management proposed the use of PIVKA-II for routine follow-up in patients with high risk for developing HCC (5,20), as well as a prognostic biomarker before surgery to predict microvascular invasion, relapse and overall poor prognosis (14)(15)(16)(17). In detail, Japanese guidelines have suggested to consider as a diagnostic marker of HCC high elevation of tumor markers, namely AFP ≥200 ng/ml and PIVKA-II ≥40 mAU/ml.…”

Non-invasive Biomarkers in Non-Alcoholic Steatohepatitisinduced Hepatocellular Carcinoma

“…In contrast, DCP was generally positive in NASH-HCC (15). Its levels were signi cantly higher at the time of HCC diagnosis compared to the time of NASH diagnosis in a small sample of Japanese patients with histologically-proven NASH (mean 34 vs. 18 mAU/mL, p=0.004).…”

“…Alpha-fetoprotein was generally positive in patients with HCV-HCC or in patients with advanced stages of HCC [15]. Mean serum AFP levels measured by enzyme-linked immunosorbent assay were signi cantly higher in patients with HCV-HCC than in patients with NASH-HCC, although a large degree of within-group variability was observed in each group [16].…”

Serum levels of anti‑sperm‑associated antigen 9 antibody are elevated in patients with hepatocellular carcinoma

“…A recent meta-analysis of the diagnostic value of AFP in HCC determined a pooled sensitivity of 66%, a specificity of 86% and an AUC value of 0.87 (37). The combination of AFP with DCP produced a sensitivity of 55% for the detection of early-stage HCC and 78% for the diagnosis of all stages of HCC, with cut-off values of 10 ng/ml for AFP and 5 ng/ml for DCP (38). The addition of AFP-L3 led to a further enhancement in sensitivity to 84% (39).…”