联合检测血清AFP、AFP-L3%和PIVKA-Ⅱ水平早期诊断和判断原发性肝癌患者预后临床价值探讨

Clinical implication of serum AFP,AFP-L3%and PIVKA-II in early diagnosing and predicting prognosis of patients with primary liver cancer

目的 探讨联合检测血清甲胎蛋白(AFP)、甲胎蛋白异质体3比率(AFP-L3%)和维生素K拮抗剂诱导蛋白-Ⅱ(PIVKA-Ⅱ)早期诊断和判断原发性肝癌(PLC)患者预后的临床价值。方法 2016年1月~2018年12月我院收治的PLC患者87例、乙型肝炎肝硬化患者79例、慢性乙型肝炎患者73例和健康体检者65例,所有PLC患者均接受经肝动脉化疗栓塞术(TACE)治疗,随访3年。采用化学发光免疫分析法检测血清AFP和PIVKA-Ⅱ水平,采用免疫荧光法检测血清AFP-L3。应用Logistic回归分析影响PLC患者3 a生存率的独立危险因素,应用受试者工作特征曲线(ROC)下面积(AUC)评估血清指标预测PLC患者预后的价值。结果 PLC组血清AFP、AFP-L3%和PIVKA-Ⅱ水平分别为(402.5±95.3)μg/L、(12.9±3.1)和(824.5±82.1) mAU/mL,显著高于乙型肝炎肝硬化组【分别为(17.9±2.6)μg/L、(8.6±1.2)和(30.4±3.2)mAU/mL,P<0.05】或慢性乙型肝炎组【分别为(20.3±6.4)μg/L、(5.4±0.9)和(29.8±3.0)mAU/mL,P<0.05】或健康体检组【分别为(2.2±0.1)μg/L、(2.7±0.4)和(26.3±3.4)mAU/mL,P<0.05】;52例死亡组血清AFP、AFP-L3%和PIVKA-Ⅱ水平分别为(447.1±71.2)μg/L、(14.1±2.2)和(883.9±50.8)mAU/mL,显著高于35例生存组【分别为(336.2±58.4)μg/L、(11.0±1.8)和(736.2±37.0)mAU/mL,P<0.05】;单因素分析显示,TNM分期、Child分级、肝外转移、血清AFP、AFP-L3%和PIVKA-Ⅱ水平均会影响PLC患者预后(P<0.05);多因素Logistic回归分析显示,TNMⅢ/Ⅳ期、Child C级、肝外转移、血清AFP≥410.5μg/L、AFP-L3%≥12.1和PIVKA-Ⅱ≥807.2 mAU/mL是影响PLC患者预后的独立危险因素(P<0.05);ROC曲线分析显示,血清AFP、AFP-L3%和PIVKA-Ⅱ联合预测PLC患者3 a预后的AUC为0.908,显著高于三者单独预测的0.763、0.830和0.792(P<0.05)。结论 联合检测血清AFP、AFP-L3%和PIVKA-Ⅱ水平可以帮助诊断PLC,并可能据此判断TACE治疗患者的预后,具有很大的临床意义。

Objective The aim of this study was to investigate the clinical implication of serum alpha-fetoprotein(AFP),alpha-fetoprotein-L-3 ratio(AFP-L3%)and protein induced by vitamin K antagonist-Ⅱ(PIVKA-Ⅱ)in early diagnosing and predicting prognosis of patients with primary liver cancer(PLC).Methods A total of 87 patients with PLC,79 patients with hepatitis B cirrhosis,73 patients with chronic hepatitis B and 65 healthy persons were enrolled in our hospital between January 2016 and December 2018.All PLC patients underwent transcatheter arterial chemoembolization(TACE)and were followed-up for 3 years.Serum AFP and PIVKA-Ⅱ levels were detected by chemiluminescence immunoassay,and serum AFP-L3 level was assayed by immumofluorescence.The independent risk factors of impacting 3-year survival in patients with PLC were analyzed by Logistic regression analysis,and the prognostic value of serum AFP,AFP-L3%and PIVKA-Ⅱ levels was evaluated by the area under the receiver operating characteristic(ROC)curves(AUC).Results Serum AFP,AFP-L3%and PIVKA-Ⅱ levels in patients with PLC were (402.5±95.3)μg/L,(12.9±3.1)and(824.5±82.1)mAU/mL,significantly higher than[(17.9±2.6)μg/L,(8.6±1.2)and(30.4±3.2)mAU/mL,P<0.05]in patients with liver cirrhosis or[(20.3±6.4)μg/L,(5.4±0.9)and(29.8±3.0)mAU/mL,P<0.05]in patients with CHB or[(2.2±0.1)μg/L,(2.7±0.4)and(26.3±3.4)mAU/mL,P<0.05]in healthy individuals;serum AFP,AFP-L3%and PIVKA-Ⅱ levels in 52 dead patients with PLC one month after TACE were(447.1±71.2)μg/L,(14.1±2.2)and(883.9±50.8)mAU/mL,much higher than[(336.2±58.4)μg/L,(11.0±1.8)and(736.2±37.0)mAU/mL,respectively,P<0.05]in 35 survivals;the univariate analysis showed that TNM staging,Child class,extrahepatic metastasis,serum AFP,AFP-L3%and PIVKA-Ⅱ levels were all influencing prognosis of patients with PLC(P<0.05),and the multivariate Logistic regression analysis showed that TNM staging III-IV,Child class C,extrahepatic metastasis,serum AFP≥410.5μg/L,AFP-L3%≥12.1 and PIVKA-Ⅱ≥807.2 mAU/mL were all independent risk factors for poor prognosis of patients with PLC(P<0.05);the ROC analysis showed that the AUC was 0.908 when combination of serum AFP,AFP-L3%and PIVKA-Ⅱ level detection in predicting the 3-year survival of patients with PLC,greatly superior to any parameter alone(the AUC were 0.763,0.830 or 0.792,respectively,P<0.05).Conclusion The combination detection of serum AFP,AFP-L3%and PIVKA-Ⅱ levels could help diagnose and early predict prognosis of patients with PLC after TACE treatment.