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.
背景与目的：肝细胞癌是全球癌症死亡的第二大原因。目前排除肝癌的金标准是结合六个月影像学检查与甲胎蛋白血清水平检测。维生素K缺乏诱导蛋白已被提议作为潜在的肝癌筛查生物标志物。本研究旨在评估PIVKA-II作为肝癌诊断标志物的作用，以及PIVKA-II水平与肝癌分期的相关性。方法：对意大利患者的血清样本进行PIVKA-II水平检测。研究人群包括80例肝癌患者、111例肝硬化患者和111例慢性丙型肝炎患者。结果：从慢性丙型肝炎患者到肝癌患者，血清PIVKA-II水平呈渐进性升高。在肝癌组中，根据巴塞罗那临床肝癌分期系统评估，疾病晚期（BCLC-B期对比BCLC-A期对比BCLC-0期）患者的PIVKA-II值更高。约登指数分析确定>37 mAU/mL为最佳阈值，此时敏感性与特异性达到最优组合（分别为80%和76%）；而AFP在最佳截断值5.2 ng/mL时特异性为53%，敏感性为78%。PIVKA-II与AFP联合检测的阳性预测值和阴性预测值分别达到73.9%和94.2%。结论：与对照组相比，肝癌患者的PIVKA-II水平显著升高，且在晚期肝癌患者中升高更为明显。PIVKA-II的诊断性能似乎比AFP更敏感，而PIVKA-II与AFP联合检测可获得最佳诊断准确率，阳性预测值达73.9%，阴性预测值达94.2%，从而提升了单一标志物的诊断能力。
Diagnostic Performance of PIVKA-II in Italian Patients with Hepatocellular Carcinoma
肿瘤(癌症)患者之家