血清异常凝血酶原Ⅱ对HBV相关肝细胞癌的诊断价值

Clinical value of serum PIVKA-Ⅱ in diagnosis of HBV-related hepatocellular carcinoma

目的研究血清AFP、维生素K缺乏或拮抗剂Ⅱ诱导蛋白(PIVKA-Ⅱ)单独或联合使用对HBV相关肝细胞癌(HCC)的临床诊断价值。方法选取2016年2月-2017年6月于徐州医科大学附属医院感染科实验室进行血清学检测的HBV相关HCC患者200例(其中手术治疗的患者80例)、乙型肝炎肝硬化患者143例、重度慢性乙型肝炎患者65例、慢性乙型肝炎肝衰竭患者42例,比较4组患者的AFP、PIVKA-Ⅱ水平。符合正态分布的计量资料多组间比较采用方差分析;不符合正态分布的计量资料多组间比较采用Krsukal-Wallis H检验,进一步两两比较采用Mann-Whitney U检验。计数资料组间比较采用χ~2检验。采用二元logistic进行逐步回归分析得出2项指标联合预测因子的新变量,利用受试者工作特征曲线计算AFP、PIVKA-Ⅱ单独或联合诊断HBV相关HCC的曲线下面积(AUC),AUC的比较采用De Long检验。结果 HBV相关HCC患者的AFP、PIVKA-Ⅱ水平高于其他3组,差异均有统计学意义(Z值分别为-9.432、-6.369、-2.158、-13.202、-9.609、-7.584,P值均<0.05)。重度慢性乙型肝炎组及慢性乙型肝炎肝衰竭组的PIVKA-Ⅱ水平明显高于乙型肝炎肝硬化组(Z值分别为-2.977、-2.308,P值均<0.05)。HBV相关HCC患者在手术治疗后5~7 d内的AFP、PIVKA-Ⅱ水平显著低于术前(Z值分别为-96.892、-76.997,P值均<0.05)。PIVKA-Ⅱ检测HBV相关HCC的敏感度、特异度分别为84.0%、86.4%,AFP检测的敏感度、特异度分别为81.5%、50.4%;AFP、PIVKA-Ⅱ及AFP联合PIVKA-Ⅱ检测HBV相关HCC的AUC分别为0.757、0.905、0.912,PIVKA-Ⅱ与AFP的AUC比较,差异有统计学意义(Z=6.048,P<0.001);二者联合对HBV相关HCC的临床诊断价值最高,明显高于AFP单独诊断价值(Z=7.814,P<0.001)。结论血清PIVKA-Ⅱ水平对HBV相关HCC的诊断价值优于AFP,二者联合检测能提高HCC的检出率,降低误诊率。

Objective To evaluate the clinical value of serum protein induced by vitamin K absence or antagonist-Ⅱ（ PIVKA-Ⅱ） and alpha-fetoprotein（ AFP）,alone or in combination,in the diagnosis of hepatitis B virus（ HBV）-related hepatocellular carcinoma（ HCC）. Methods A total of 450 patients with HBV infection,who underwent serological tests in the Department of Infectious Diseases,The Affiliated Hospital of Xuzhou Medical University,from February 2016 to June 2017,were enrolled in our hospital,including 200 patients with HBV-related HCC（ 80 surgically treated cases）,143 patients with hepatitis B cirrhosis,65 patients with severe chronic hepatitis B（ CHB）,and 42 CHB patients with liver failure. The serum levels of PIVKA-Ⅱ and AFP were compared between the four groups. An analysis of variance was used to compare normally distributed continuous data between multiple groups; the Kruskal-Wallis H test was used to compare non-normally distributed continuous data between multiple groups,and the Mann-Whitney U test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. A binary stepwise logistic regression was used to obtain a new variable as a combination of PIVKA-Ⅱ and AFP. The receiver operating characteristic（ ROC） curve was used to calculate the area under the ROC curve（ AUC） of AFP and PIVKA-Ⅱ,alone or in combination,in the diagnosis of HBV-related HCC,and the De Long test was used for comparison of AUC between these variables. Results The HBV-related HCC patients had significantly higher PIVKA-Ⅱ and AFP levels than other groups（ Z =-9. 432,-6. 369,-2. 158,-13. 202,-9. 609,and-7. 584,all P〈0. 05）. The PIVKA-Ⅱ levels of the patients with severe CHB and CHB patients with liver failure were significantly higher than that of the patients with hepatitis B cirrhosis（ Z =-2. 977 and-2. 308,both P〈0. 05）. The HBV-related HCC patients showed significant reductions in AFP and PIVKA-Ⅱ levels within 5-7 days after surgical treatment（ Z =-96. 892 and-76. 997,both P〈0. 05）. In the diagnosis of HBV-related HCC,PIVKA-Ⅱ had 84. 0% sensitivity and 86. 4% specificity,and AFP had 81. 5% sensitivity and 50. 4%specificity. The AUCs of AFP,PIVKA-Ⅱ,and a combination of AFP and PIVKA-Ⅱ in the diagnosis of HBV-related HCC were0. 757,0. 905,and 0. 912,respectively; there were significant differences in AUC between PIVKA-Ⅱ and AFP（ Z = 6. 048,P〈0. 001）and between AFP and a combination of AFP and PIVKA-Ⅱ（ Z = 7. 814,P〈0. 001）. A combination of AFP and PIVKA-Ⅱ had the highest diagnostic efficiency for HBV-related HCC. Conclusion Serum PIVKA-II has a better diagnostic value for HBV-related HCC than AFP,and a combination of the two can increase the detection rate of HCC and reduce the rate of misdiagnosis.