Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France; INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France.
INSERM UMR 1149, Inflammation Research Center, Paris-Diderot University, Paris, France; Department of Hepatobiliary Surgery and Liver Transplantation, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.
J Hepatol. 2015 Apr;62(4):848-54. doi: 10.1016/j.jhep.2014.11.005. Epub 2014 Nov 11.
BACKGROUND & AIMS: Prothrombin induced by vitamin K absence-II (PIVKA-II) is a diagnostic and surveillance marker for HCC mainly used in Asia, and has also been shown to be a predictor of microvascular invasion (MVI), a major prognostic factor in HCC. However, experience with PIVKA-II in Europe remains limited.
In a French cohort, we conducted a case-control study to compare the performances of α-fetoprotein (AFP) and PIVKA-II serum levels for diagnosis of early stage HCC, and we determined the value of PIVKA-II serum and tissue expression in pre-operative detection of MVI. 43 cirrhotic control patients and 85 HCC cases were included, of which 54 (63.5%) had early stage HCC (n=22 very early, n=32 early). PIVKA-II tissue expression was assessed by immunohistochemistry in HCC surgical samples.
For the diagnosis of early HCC, PIVKA-II had a sensitivity of 77% and a specificity of 82% at a cut-off of 42 mAU/ml, vs. 61% and 50% for AFP at a cut-off of 5.5 ng/ml (AUC 0.81 vs. 0.58, respectively). A PIVKA-II level >90 mAU/ml was an independent predictor of MVI (HR 3.5; 95% CI 1.08-11.8; p=0.043). High PIVKA-II tissue expression was significantly associated with the presence of MVI (p=0.001). When combining PIVKA-II immunostaining with the PIVKA-II serum level, sensitivity and specificity for the diagnosis of MVI increased from 70% to 87% and 63% to 90%, respectively.
PIVKA-II was more efficient than AFP for the diagnosis of early HCC, and could be used as a predictive biomarker of MVI.
维生素 K 缺乏诱导的凝血酶原(PIVKA-II)是 HCC 的一种诊断和监测标志物,主要在亚洲使用,也被证明是微血管侵犯(MVI)的预测因子,MVI 是 HCC 的一个主要预后因素。然而,在欧洲,人们对 PIVKA-II 的经验仍然有限。
在法国的一个队列中,我们进行了一项病例对照研究,比较了血清 AFP 和 PIVKA-II 水平对早期 HCC 的诊断性能,并确定了 PIVKA-II 血清和组织表达在术前检测 MVI 中的价值。共纳入 43 例肝硬化对照患者和 85 例 HCC 病例,其中 54 例(63.5%)为早期 HCC(n=22 例非常早期,n=32 例早期)。通过免疫组化检测 HCC 手术样本中的 PIVKA-II 组织表达。
对于早期 HCC 的诊断,当 PIVKA-II 的截断值为 42 mAU/ml 时,其灵敏度为 77%,特异性为 82%,而 AFP 的截断值为 5.5 ng/ml 时,灵敏度为 61%,特异性为 50%(AUC 分别为 0.81 和 0.58)。PIVKA-II 水平>90 mAU/ml 是 MVI 的独立预测因子(HR 3.5;95%CI 1.08-11.8;p=0.043)。高 PIVKA-II 组织表达与 MVI 的存在显著相关(p=0.001)。当将 PIVKA-II 免疫染色与 PIVKA-II 血清水平相结合时,诊断 MVI 的灵敏度和特异性分别从 70%提高到 87%,从 63%提高到 90%。
PIVKA-II 对早期 HCC 的诊断比 AFP 更有效,并且可以用作 MVI 的预测生物标志物。