血清异常凝血酶原对乙型肝炎病毒相关肝细胞癌生物学特性的预测价值  

The significance of prothrombin induced by vitamin K absence-Ⅱin predicting the biological characteristics of hepatitis B virus-associated hepatocellular carcinoma

作　　者：罗俐梅[1] 苏真珍[1] 赵文玲 蒙立业 李立新[1] 蔡蓓[1] 白杨娟[1] 黄卓春[1] LUO Limei;SU Zhenzhen;ZHAO Wenling;MENG Liye;LI Lixin;CAI Bei;BAI Yangjuan;HUANG Zhuochun(Department of Laboratory Medicine,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China)

机构地区：[1]四川大学华西医院实验医学科,成都610041

出　　处：《华西医学》2020年第12期1471-1477,共7页West China Medical Journal

基　　金：国家自然科学基金(81702002);四川省科学技术厅重点研发项目(2018FZ0106,2019YFS0284,2019YFS0287,2019YFS0370)。

摘　　要：目的探讨血清异常凝血酶原(prothrombin induced by vitamin K absence-Ⅱ,PIVKA-Ⅱ)检测对乙型肝炎病毒(hepatitis B virus,HBV)相关肝细胞癌(hepatocellular carcinoma,HCC)生物学特性的预测价值。方法回顾性纳入2017年6月—2018年12月在四川大学华西医院新近诊断并接受手术切除治疗的HBV相关HCC患者394例。从病历中收集肿瘤大小、肿瘤数目、肿瘤细胞分化程度、有无微血管浸润、有无远处转移、有无门静脉癌栓等临床信息;收集患者诊断时和手术前实验室检查结果,包括甲胎蛋白、PIVKA-Ⅱ、谷丙转氨酶、谷草转氨酶、γ-谷氨酰转肽酶等,分析PIVKA-Ⅱ水平与肿瘤生物学特性间的关系。非正态分布资料采用中位数(下四分位数,上四分位数)表示。结果与术前低血清PIVKA-Ⅱ水平(≤40 mAU/mL)的HCC患者相比,术前高血清PIVKA-Ⅱ水平(>40 mAU/mL)的HCC患者肿瘤直径更大[5.00(3.00,9.00)vs.2.50(1.63,4.95)cm,P<0.001],更容易形成门静脉癌栓(16.61%vs.3.75%,P=0.003)和微血管浸润(43.67%vs.11.11%,P<0.001),巴塞罗那临床肝癌(Barcelona Clinic Liver Cancer,BCLC)分期更严重(P<0.001),且甲胎蛋白[186.05(6.86,1210.00)vs.17.83(4.33,231.95)ng/mL,P<0.001]、谷丙转氨酶[38.00(26.00,66.25)vs.32.00(22.00,51.00)U/L,P=0.018]、谷草转氨酶[42.00(30.00,76.00)vs.34.00(25.50,48.25)U/L,P<0.001]、γ-谷氨酰转肽酶[71.00(39.00,165.50)vs.55.50(25.00,93.00)U/L,P=0.005]水平更高。BCLC分期0期的HCC患者,PIVKA-Ⅱ阳性率仅为51.35%。多因素logistic回归分析显示,PIVKA-Ⅱ>40 mAU/mL是微血管浸润的独立预测因子[比值比=6.588,95%置信区间(1.645,26.383),P=0.008],且PIVKA-Ⅱ水平预测微血管浸润的受试者工作特征曲线下面积为0.761[95%置信区间(0.693,0.830)],灵敏度为66.22%,特异度为79.06%。结论在HBV相关HCC患者,高PIVKA-Ⅱ水平与不良的肿瘤生物学特性有关,并且是肿瘤微血管浸润的独立危险因素。Objective To explore the predictive value of serum prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)detection for the biological characteristics of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC).Methods This retrospective study included 394 patients with HBV-related HCC who were newly diagnosed and treated with surgical resection in West China Hospital of Sichuan University between June 2017 and December 2018.Their clinical information such as tumor size,tumor number,tumor cell differentiation,presence of microvascular invasion(MVI),distant metastasis,and portal vein tumor thrombus was collected from the medical record.The laboratory test results of patients during diagnosis and before surgery were collected,including alpha-fetoprotein(AFP),PIVKA-Ⅱ,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(γ-GGT),etc.,and the relationships between PIVKA-Ⅱlevels and tumor biological characteristics were analyzed.Non-normal continuous variables were presented as medium(lower quartile,upper quartile).Results Compared with the patients with low HCC serum PIVKA-Ⅱlevels(≤40 mAU/mL),patients with high serum PIVKA-Ⅱlevels(>40 mAU/mL)had larger tumor diameters[5.00(3.00,9.00)vs.2.50(1.63,4.95)cm,P<0.001],more severe Barcelona Clinic Liver Cancer(BCLC)stage(P<0.001),and higher AFP[186.05(6.86,1210.00)vs.17.83(4.33,231.95)ng/mL,P<0.001],ALT[38.00(26.00,66.25)vs.32.00(22.00,51.00)U/L,P=0.018],AST[42.00(30.00,76.00)vs.34.00(25.50,48.25)U/L,P<0.001],andγ-GGT[71.00(39.00,165.50)vs.55.50(25.00,93.00)U/L,P=0.005],and were more likely to form portal vein tumor thrombi(16.61%vs.3.75%,P=0.003)and MVI(43.67%vs.11.11%,P<0.001).In BCLC stage 0 HCC patients,the positive rate of PIVKA-Ⅱwas only 51.35%.Multivariate logistic regression analysis showed that PIVKA-Ⅱ>40 mAU/mL was an independent predictor of MVI[odds ratio=6.588,95%confidence interval(CI)(1.645,26.383),P=0.008].The area under receiver operating characteristic curve of PIVKA-Ⅱlevel predicting MVI was 0.761[

关 键 词：乙型病毒性肝炎 肝细胞癌 异常凝血酶原 微血管浸润 

分 类 号：R735.7[医药卫生—肿瘤]