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

Simple Summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths globally. Current gold-standard screening methods include imaging every six months and measuring alpha-fetoprotein (AFP) levels. This study evaluates Protein Induced by Vitamin K Absence-II (PIVKA-II) as a diagnostic biomarker for HCC and its correlation with disease stage. PIVKA-II levels progressively increase from chronic hepatitis C to liver cirrhosis and are highest in HCC patients, with levels correlating to advanced HCC stages based on the Barcelona Clinic Liver Cancer system. The optimal PIVKA-II threshold (>37 mAU/mL) achieved 80% sensitivity and 76% specificity, outperforming AFP, which had 53% specificity and 78% sensitivity at a cut-off of 5.2 ng/mL. Combining PIVKA-II and AFP improved diagnostic accuracy, achieving a positive predictive value of 73.9% and a negative predictive value of 94.2%. The findings suggest that PIVKA-II performs better than AFP alone and that their combined use enhances diagnostic accuracy, especially for advanced disease stages. 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. [ABSTRACT FROM AUTHOR]