血清异常凝血酶原和甲胎蛋白在肝细胞肝癌诊疗中的应用研究

Application Research of Serum PIVKA-Ⅱ and AFP in the Diagnosis and Treatment of Primary Liver Cancer

目的探讨血清异常凝血酶原(PIVKA-Ⅱ)和甲胎蛋白(AFP)对肝细胞肝癌患者的疾病诊断及疗效监测的应用价值。方法收集2017年10月至2018年2月就诊于西京医院的肝细胞肝癌患者56例,肝硬化患者54例,慢性肝炎患者40例,胃癌、肠癌、胰腺癌等其他肿瘤患者32例,健康体检者35例,其中56例HCC患者进行术后随访,分别用化学发光法和电化学发光法检测各组血清PIVKA-Ⅱ和AFP水平,利用受试者工作特征曲线(ROC曲线)分析两者单独及联合检测对鉴别诊断HCC与肝良性病的曲线下面积(ROC-AUC),分析三者对HCC患者诊断的灵敏度及特异性,比较两者在HCC患者治疗前后血清水平的变化。结果 HCC组PIVKA-Ⅱ及AFP水平均明显高于肝硬化组、慢性肝炎组、其他肿瘤组及健康对照组(P均<0. 001)。肝硬化组、慢性肝炎组、其他肿瘤组及健康对照组PIVKA-Ⅱ水平无差异,AFP在肝硬化组的水平较健康对照组高,差异有统计学意义(U=630.0,P<0.001)。ROC曲线显示PIVKA-Ⅱ、AFP单独及联合检测对鉴别HCC和肝良性病的曲线下面积分别为0. 972、0. 892及0. 980,鉴别诊断的最佳临界值分别为64. 50mAU/mL和12.09ng/mL;血清PIVKA-Ⅱ诊断HCC的灵敏度为94. 64%高于AFP (76. 79%,χ~2=7. 29, P<0. 05),联合检测的灵敏度最高为98.21%,与PIVKA-Ⅱ单独检测的灵敏度差异无统计学意义(P>0.05),单独检测与联合检测的特异性比较均无统计学差异(P>0. 05); HCC患者治疗后血清PIVKA-Ⅱ水平较治疗前显著下降,差异有统计学意义(t=4. 31,P <0. 001),AFP治疗后水平亦较治疗前下降,但差异无统计学意义(t=1. 82,P>0. 05)。结论血清PIVKA-Ⅱ单独检测在对HCC的诊断、鉴别诊断及疗效评估方面均优于AFP,两者联合检测诊断HCC可在不降低特异性的情况下进一步提高灵敏度,弥补单项检测的不足。

Objective To explore the application value of abnormal prothrombin (PIVKA-Ⅱ)and alpha fetoprotein (AFP)in the diagnosis and treatment of primary liver cancer. Methods We collected patients who were recruited by Xijing Hospital from October 2017 to February 2018.The serum levels of PIVKA-Ⅱ and AFP were measured by both chemiluminescence assay (CLIA)and electrochemiluminescence assay (ECLA)in patients with HCC (n=56),cirrhosis (n=54),chronic hepatitis (n=40),other tumor patients such as gastric cancer,colorectal cancer,pancreatic cancer (n=32)and healthy subjects (n=35).56 patients with HCC were followed up.We then analyzed the areas under the receiver operating characteristic curves (ROC- AUC)and to compared the sensitivities and specificities among single PIVKA-Ⅱ or AFP assay,and the combined detection.We also compared the serum level changes of the two indicators in HCC patients before and after treatment. Results The serum levels of both PIVKA-Ⅱand AFP in HCC group were higher than that in cirrhosis,chronic hepatitis,other tumor group and healthy subjects group( P <0.001).The serum level of PIVKA-Ⅱamong other groups were not significantly different ( P > 0.05).AFP in cirrhosis group was higher than that in healthy subjects group( U =630.0, P <0.001).The ROC- AUCs of the single PIVKA-Ⅱor AFP assay and the combined detection in differentia diagnosis of HCC and benign liver disease were 0.972 ,0.892 and 0.980,respectively.The optimal thresholds for differential diagnosis were 64.50mAU/ml and 12.09ng/mL,respectively.The sensitivity of PIVKA-Ⅱ(94.64%)was higher than that of AFP( 76.79%,χ 2= 7.29, P < 0.05)in diagnosing HCC and the sensitivity of combined detection of PIVKA-Ⅱ and AFP was the highest(98.21%),with no significant difference compared with that of single PIVKA-Ⅱassay( P > 0.05 ).There was no significant difference in specificities among them ( P >0.05).The mean values of PIVKA-Ⅱin HCC after the treatment was significantly lower than that before the treatment ( t =4.31, P <0.001),while there was no significant difference( t =1.822, P >0.05) between the serum level of AFP after the treatment and that before the treatment. Conclusion Single PIVKA-Ⅱ detection was superior to AFP in the diagnosing HCC and monitoring treatment effects.The combined detection of PIVKA-Ⅱ and AFP can improve the sensitivity in diagnosing HCC without reducing the specificity,which can make up the deficiency of single detection.