化学发光微粒子免疫法测定维生素K缺乏诱导蛋白成人参考区间的建立

Establishment the reference interval of adult protein-induced vitamin K absence/antagonist Ⅱ by chemiluminescent microparticle immunoassay

目的建立绵阳地区化学发光微粒子免疫法(CMIA)测定血清维生素K缺乏诱导蛋白(PIVKA-Ⅱ)的成人参考区间,并探讨病毒性肝炎、肝硬化和肝细胞肝癌(HCC)患者血清PIVKA-Ⅱ水平的变化。方法采用化学发光微粒子免疫法测定674名表观健康者、147例病毒性肝炎患者、90例肝硬化患者及98例HCC患者血清PIVKA-Ⅱ水平。采用x±1.96s方式建立PIVKA-Ⅱ的参考区间。采用受试者工作特征(ROC)曲线评估PIVKA-Ⅱ诊断肝炎、肝硬化及HCC的效能。结果674名表观健康者血清PIVKA-Ⅱ测定值呈近似正态分布(z=1.428,P=0.034),男、女性之间血清PIVKA-Ⅱ水平差异无统计学意义(P>0.05),按年龄分组(18~30岁组、31~44岁组、45~59岁组、60~69岁组、≥70岁组)后各年龄组之间血清PIVKA-Ⅱ水平差异均无统计学意义(P>0.05)。合并数据后采用x±1.96s方式建立的参考区间为8.75~36.72 U/L。与正常对照组比较,病毒性肝炎组、肝硬化组和HCC组血清PIVKA-Ⅱ水平均明显升高(P<0.001)。HCC组血清PIVKA-Ⅱ水平明显高于病毒性肝炎组、肝硬化组(P<0.001),而病毒性肝炎组与肝硬化组之间差异无统计学意义(P>0.05)。ROC曲线分析结果显示,血清PIVKA-Ⅱ诊断病毒性肝炎、肝硬化和HCC的曲线下面积分别为0.656、0.663、0.900,最佳临界值分别为27.27、29.86和40.36 U/L,敏感性分别为49.7%、52.2%和80.6%,特异性分别为75.7%、80.8%和94.5%。结论初步建立了绵阳地区CMIA检测血清PIVKA-Ⅱ的成人参考区间。PIVKA-Ⅱ在病毒性肝炎和肝硬化等非肝癌患者中也有不同程度的升高,因此不宜单独作为HCC标志物使用。

Objective To establish the reference interval of adult protein-induced vitamin K absence/antagonistⅡ(PIVKA-Ⅱ)in Mianyang by chemiluminescent microparticle immunoassay(CMIA),and to investigate the change of PIVKA-Ⅱ levels in patients with viral hepatitis,cirrhosis and hepatocellular carcinoma(HCC).Methods Serum PIVKA-Ⅱ levels were determined by CMIA in 674 healthy subjects,147 viral hepatitis patients,90 cirrhosis patients and 98 HCC patients.The reference interval of PIVKA-Ⅱ was established by x±1.96s.The diagnostic efficiency of PIVKA-Ⅱ to viral hepatitis,cirrhosis and HCC was evaluated by receiver operating characteristic(ROC)curve.Results The results of serum PIVKA-Ⅱ determination of 674 healthy subjects showed approximate normal distribution(z=1.428,P=0.034),and there was no statistical significance between males and females(P>0.05).The subjects were classified according to ages(18-30-year-old,31-44-yearold,45-59-year-old,60-69-year-old and ≥70-year-old groups),and there was no statistical significance in these groups(P>0.05).The data were merged,and the reference interval established by x±1.96s was 8.75-36.72 U/L.Compared to healthy control group,serum PIVKA-Ⅱ levels in viral hepatitis group,cirrhosis group and HCC group increased(P<0.001).Serum PIVKA-Ⅱ levels in HCC group were higher than those in viral hepatitis group and cirrhosis group(P<0.001),and there was no statistical significance between viral hepatitis group and cirrhosis group(P>0.05).By ROC curve analysis,the areas under curve(AUC)of serum PIVKA-Ⅱ for viral hepatitis,cirrhosis and HCC were 0.656,0.663 and 0.900,and the optimal cut-off values were 27.27,29.86 and 40.36 U/L,the sensitivities were 49.7%,52.2% and 80.6%,and the specificities were 75.7%,80.8% and 94.5%,respectively.Conclusions The reference interval of serum adult PIVKA-Ⅱ by CMIA in Mianyang has preliminarily been established.PIVKA-Ⅱ increases in various degrees in patients with non-liver cancer,such as viral hepatitis and cirrhosis,and it should not be used alone as a marker of HCC.