Saitta Carlo, Raffa Giuseppina, Alibrandi Angela, Brancatelli Santa, Lombardo Daniele, Tripodi Gianluca, Raimondo Giovanni, Pollicino Teresa
Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina Department of Clinical and Experimental Medicine Department of Economics Department of Human Pathology, University of Messina, Messina, Italy.
Medicine (Baltimore). 2017 Jun;96(26):e7266. doi: 10.1097/MD.0000000000007266.
Protein induced by vitamin K absence-II (PIVKA-II) is a potential screening marker for hepatocellular carcinoma (HCC). Limited data are available about its utility in discriminating neoplastic from regenerative nodules at ultrasonography (US) evaluation in cirrhotic patients. Aim of this study was to investigate the diagnostic utility of PIVKA-II in cases showing liver nodules of uncertain diagnosis at US.Ninety cirrhotics with US evidence of liver nodule(s) were enrolled. All patients underwent blood sampling within 1 week of US and were thereafter followed up. HCC was confirmed in 40/90 cases, and in all cases it was in a very early/early stage. All sera were tested for PIVKA-II and alpha-fetoprotein (AFP) at the end of follow-up. PIVKA-II at a cut off of 60 mAU/mL was significantly associated with HCC at both univariate and multivariate analysis (P = .016 and P = .032, respectively). AFP at a cut off of 6.5 ng/mL was not associated with HCC at univariate analysis (P = .246). ROC curves showed that PIVKA-II had 60% sensitivity, 88% specificity, 80% positive predictive value (PPV), and 73% negative predictive value (NPV), whereas AFP had 67% sensitivity, 68% specificity, 63% PPV, and 72% NPV. AUROC curves showed that the combination of both biomarkers increased the diagnostic accuracy for HCC (AUC 0.76; sensitivity 70%, specificity 94%, PPV 91%, and NPV 79%).In conclusion, PIVKA-II is a useful tool for the diagnostic definition of US-detected liver nodules in cirrhotic patients, and it provides high diagnostic accuracy for HCC when combined with AFP.
维生素K缺乏诱导蛋白-II（PIVKA-II）是肝细胞癌（HCC）的一种潜在筛查标志物。关于其在肝硬化患者超声（US）评估中鉴别肿瘤性结节与再生结节的效用，现有数据有限。本研究的目的是探讨PIVKA-II在US检查显示肝脏结节诊断不确定的病例中的诊断效用。
纳入了90例有肝脏结节US证据的肝硬化患者。所有患者在US检查后1周内进行血液采样，之后进行随访。90例中有40例确诊为HCC，且所有病例均处于极早期/早期阶段。随访结束时检测所有血清中的PIVKA-II和甲胎蛋白（AFP）。单因素和多因素分析中，PIVKA-II截断值为60 mAU/mL时均与HCC显著相关（分别为P = .016和P = .032）。AFP截断值为6.5 ng/mL时，单因素分析与HCC无相关性（P = .246）。ROC曲线显示，PIVKA-II的敏感性为60%，特异性为88%，阳性预测值（PPV）为80%，阴性预测值（NPV）为73%；而AFP的敏感性为67%，特异性为68%，PPV为63%，NPV为72%。AUROC曲线显示，两种生物标志物联合使用可提高HCC的诊断准确性（AUC 0.76；敏感性70%，特异性94%，PPV 91%，NPV 79%）。
总之，PIVKA-II是肝硬化患者US检测肝脏结节诊断定义的有用工具，与AFP联合使用时对HCC具有较高的诊断准确性。
