标题：PIVKA-Ⅱ与AFP检测对原发性肝癌的诊断价值

      作者：周泉宇 1，吴红樱 2，雷泽华 1，高峰畏 1，蒋康怡 1    (乐山市人民医院肝胆外科 1、病理科 2，四川 乐山 614000)

      卷次： 2018年29卷7期

      【摘要】 目的 探究异常凝血酶原(PIVKA-Ⅱ)与甲胎蛋白(AFP)对原发性肝癌(HCC)的诊断价值。方法 将2012年1月1日至2016年12月31日乐山市人民医院肝胆外科就诊的128例患者纳入研究，其中原发性肝癌85例，肝硬化 43例。测定术前、术后血清及组织中 PIVKA-Ⅱ及AFP的浓度。运用受试者工作特性曲线(ROC)分析PIVKA-II及AFP的检测效能，确定其检测HCC的临界值及敏感度和特异度。对HCC患者进行变量分析，以确定肿瘤组织微血管侵袭性(MVI)的潜在预测因子。对术中采集的肿瘤及各相邻非瘤肝块进行免疫组化半定量分析并予以评分。结果 HCC组患者的PIVKA-Ⅱ中位浓度为136 mAU/mL，明显高于肝硬化组的26 mAU/mL，差异有显著统计学意义(P<0.01)；而两组患者的AFP中位浓度比较差异无统计学意义(P>0.05)。血清PIVKA-Ⅱ诊断HCC的曲线下面积为[0.544(95%CI：0.444~0.645)]，优于AFP诊断HCC的能力[0.453(95%CI：0.350~0.555)]。对于HCC的诊断，PIVKA-Ⅱ检测早期HCC的最佳临界值(Cut-off)为42 mAU/mL，此时检测HCC敏感度为77%，特异度为82%；AFP检测早期HCC的(Cut-off)值为5.8 ng /mL，此时其检测HCC的灵敏度为61%，特异度为50%。PIVKA-Ⅱ>90 mAU/mL(HR 3.5；95%CI，1.08~11.8；P=0.043)和中度/低分化肿瘤(HR 3.4；95%CI，1.04~11.05；P=0.037)是MVI独立的预测因素。结论 PIVKA-Ⅱ比AFP对早期原发性肝癌有更高的敏感性和特异性。此外，将PIVKA-Ⅱ血清水平和组织表达作为MVI的术前生物标志物使用，可以提高早期原发性肝癌的诊断效率，对肿瘤预后评估有较高的临床应用价值。
      【关键词】 原发性肝癌；甲胎蛋白；异常凝血酶原-Ⅱ；诊断
      【中图分类号】 R735.7 【文献标识码】 A 【文章编号】 1003—6350（2018）07—0960—04

Diagnostic value of prothrombin induced by vitamin K absence- Ⅱ and alpha-fetoprotein for primaryhepatocellular carcinoma.
ZHOU Quan-yu 1, WU Hong-yin 2, LEI Ze-hua 1, GAO Feng-wei 1, JIANG Kang-yi 1.Department of Hepatobiliary Surgery 1, Department of Pathology 2, Leshan People's Hospital, Leshan 614000, Sichuan, CHINA
【Abstract】 Objective To investigate the diagnostic value of prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ) and alpha-fetoprotein (AFP) in primary hepatocellular carcinoma (HCC). Methods A total of 128 pa-tients, including 85 patients with HCC and 43 cirrhotic control patients, who admitted to Department of HepatobiliarySurgery of Leshan People's Hospital from January 1, 2012 to December 31, 2016, were selected as the research objects.The values of PIVKA-Ⅱ and AFP in serum and tissue were measured before and after operation. The detection perfor-mance of PIVKA-Ⅱ and AFP was analyzed by the receiver operating characteristic curve (ROC) to determine the criti-cal value and sensitivity and specificity of the detection of HCC. Variable analysis was carried out in HCC patients to deter-mine the potential predictors of microvascular invasion (MVI). The tumor and adjacent non-tumor liver of each case wereselected for immunohistochemistry study and then graded. Results The median PIVKA-Ⅱ level was 136 mAU/mL inHCC patients versus 26 mAU/mL in control patients (P<0.01). There was no significant difference between the twogroups in the median AFP level (P>0.05). The area under the ROC curve was 0.544 (95%CI; 0.444-0.645) for PIVKA-Ⅱ,which was better than 0.453 (95%CI; 0.350-0.555) for AFP. For the diagnosis of early HCC, PIVKA-Ⅱ had a sensi-tivity of 77% and a specificity of 82% at a cut-off of 42 mAU/mL. While AFP had a sensitivity of 61% and a specifici-ty of 50% at a cut-off of 5.5 mAU/mL. PIVKA-Ⅱ level >90 mAU/mL (HR 3.5; 95% CI 1.08-11.8; P=0.043) andmoderately/poorly differentiated tumors (HR 3.4; 95%CI 1.04-11.05; P=0.037) were independent predictors of MVI.Conclusion PIVKA-Ⅱ is more sensitive and specific than AFP in the diagnosis of HCC. In addition, the use of PIV-KA-Ⅱ serum level and tissue expression as a preoperative biomarker for MVI can improve the diagnostic efficiency ofearly HCC, which has a great clinical effect on the evaluation of tumor prognosis.
      【Key words】 Primary hepatocellular carcinoma (HCC); Alpha-fetoprotein (AFP) ; Prothrombin induced by vita-min K absence-Ⅱ (PIVKA-Ⅱ); Diagnosis·论 著·doi:10.3969/j.issn.1003-6350.2018.07.023