Diagnostic Performance of PIVKA-II in Italian Patients with Hepatocellular Carcinoma

Abstract

Background and aims: Hepatocellular carcinoma (HCC) represents the second leading cause of cancer deaths worldwide. Six-month imaging along with alpha-fetoprotein (AFP) serum levels detection are the current gold standard to exclude HCC. Protein induced by vitamin K absence (PIVKA-II) has been proposed as a potential screening biomarker for HCC. This study was designed to evaluate the role of PIVKA-II as diagnostic HCC marker, and the correlation between PIVKA-II levels and HCC stage.

Methods: PIVKA-II levels were assessed on serum samples of Italian patients. The study population included 80 patients with HCC, 111 with liver cirrhosis (LC), and 111 with chronic hepatitis C (CHC).

Results: PIVKA-II serum levels progressively increase from patients with CHC to patients with HCC. In the HCC group, PIVKA-II values are higher in the more advanced stages of the disease, assessed by the Barcelona Clinic Liver Cancer (BCLC) staging system (BCLC-B vs. BCLC-A vs. BCLC-0). Youden's index analysis identified a value >37 mAU/mL as the optimal threshold for the best combination of sensitivity and specificity (80% and 76%, respectively) and, at the best cut-off of 5.2 ng/mL, AFP yielded 53% specificity and 78% sensitivity. The combination of PIVKA-II and AFP reached positive and negative predictive values of 73.9% and 94.2%, respectively.

Conclusions: PIVKA-II levels are increased in the HCC patients, compared to control groups. The increase is more evident in patients with advanced HCC. The diagnostic performance of PIVKA-II seems more sensitive than AFP while the combination of PIVKA-II and AFP resulted in the best diagnostic accuracy, reaching 73.9% positive predictive value and 94.2% negative predictive value, thus improving the diagnostic capability of the single marker.

Keywords: alpha-fetoprotein; diagnostic biomarkers; hepatocellular carcinoma; protein induced by vitamin K absence or antagonist II; surveillance.

Figure 1

PIVKA-II levels mAU/mL in 80 patients with HCC, analyzed for MELD score each blue dot represents a PIVKA-II level.

Figure 2

Receiver operating characteristic (ROC) curve for PIVKA-II as diagnostic biomarker for HCC. Blue line refers to PIVKA-II levels, green line is a reference.

Figure 3

Predictive values of the PIVKA-II. Cut-off 37.05 mAU/mL on identification of HCC patients.

Figure 4

Receiver operating characteristic (ROC) curves for PIVKA-II and AFP as diagnostic biomarkers for HCC. Blue line = PIVKA-II; green line = AFP.

Figure 5

Predictive values of the AFP. Cut-off 5.2 ng/mL for identification of HCC.

Figure 6

Predictive values of combination PIVKA-II/AFP at established cut-offs for identification of HCC patients.