PIVKA-Ⅱ、AFP和AST/ALT比值联合检测在HBV感染原发性肝癌中的诊断价值
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摘要
目的探讨肿瘤标志物异常凝血酶原(PIVKA-Ⅱ)在乙型肝炎病毒(HBV)感染的原发性肝癌患者血清中的表达水平及其联合甲胎蛋白(AFP)和谷草转氨酶(AST)/谷丙转氨酶(ALT)比值检测在HBV感染原发性肝癌诊断中的应用价值。方法收集68例HBV感染原发性肝癌患者血清,同时收集109例HBV感染的其他疾病(包括胆囊疾病8例、肝脏良性疾病94例和其他器官疾病7例)患者血清作为对照。用化学发光法检测患者血清PIVKA-Ⅱ水平,电化学发光法检测AFP水平,速率法检测AST和ALT含量,并计算AST/ALT比值。比较各肿瘤标志物在两组间的表达水平,受试者工作特征曲线(ROC)分析各肿瘤标志物单独及联合应用对HBV感染的原发性肝癌的诊断效能。结果 HBV感染的原发性肝癌组血清PIVKA-Ⅱ、AFP和AST/ALT比值水平均高于HBV感染的其他疾病,差异均具有统计学意义(P<0.01)。ROC曲线分析表明,血清PIVKA-Ⅱ、AFP和AST/ALT比值的诊断临界值分别设定为100.42mAu/mL、232.35ng/mL和1.571时,其在诊断HBV感染原发性肝癌中的ROC曲线下面积(AUC)分别为0.942、0.786和0.723,灵敏度分别为89.70%、58.80%和51.50%;特异度分别为91.70%、88.10%和79.80%。PIVKA-Ⅱ联合AST/ALT比值诊断HBV感染原发性肝癌的AUC最大,为0.955,灵敏度为86.80%,特异度为93.40%。结论 PIVKA-Ⅱ诊断HBV感染原发性肝癌的价值明显优于AFP和AST/ALT比值,同时其联合AST/ALT比值将有助于提高HBV感染原发性肝癌诊断的价值。
Objective To investigate the expression level of protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in serum of primary liver cancer patients with HBV infection and combined with alphafetoprotein(AFP)and AST/ALT ratio in the diagnosis of primary liver cancer with HBV infection.Methods Sera of 68 HBV infection patients with primary liver cancer were collected.Meanwhile,sera of 109 HBV infection patients(8 cases of gallbladder diseases,94 cases of benign liver diseases,7 csaes of other organ diseases)were collected as controls.The serum levels of PIVKA-Ⅱand AFP were detected by the method of chemiluminescent immunoassay and electrochemical luminescence respectively.The rate method was used to detect the content of AST and ALT,and the ratio of AST/ALT was calculated.Compared the expression level of tumor markers in each group,and the receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic efficacy of individual and combined application of each index in the diagnosis of primary liver cancer.Results The sera levels of PIVKA-Ⅱ,AFP and AST/ALT ratio in primary liver cancer with HBV infection group were all higher than those in control group(P<0.01).ROC curve analysis showed that with the critical value of PIVKA-Ⅱ,AFP and AST/ALT ratio in serum were 100.42 mAu/mL,232.35 ng/mL and 1.571 in the diagnosis of primary liver cancer with HBV infection,the area under the ROC curve(AUC)were 0.942,0.786 and 0.723 respectively;the sensitivity were 89.70%,58.80%and 51.50%;the specificity were 91.70%,88.10%and 79.80%.The AUC of PIVKA-Ⅱcombined with AST/ALT ratio in the diagnosis of primary liver cancer with HBV infection was 0.955,the sensitivity and specificity wree 86.80%and 93.40%respectively.Conclusion The value of PIVKA-II in the diagnosis of primary liver cancer with HBV infection is obviously better than that of AFP and AST/ALT ratio.The combined detection with AST/ALT ratio will be helpful to improve the diagnostic efficacy of primary liver cancer with HBV infection.
Objective To investigate the expression level of protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in serum of primary liver cancer patients with HBV infection and combined with alphafetoprotein(AFP)and AST/ALT ratio in the diagnosis of primary liver cancer with HBV infection.Methods Sera of 68 HBV infection patients with primary liver cancer were collected.Meanwhile,sera of 109 HBV infection patients(8 cases of gallbladder diseases,94 cases of benign liver diseases,7 csaes of other organ diseases)were collected as controls.The serum levels of PIVKA-Ⅱand AFP were detected by the method of chemiluminescent immunoassay and electrochemical luminescence respectively.The rate method was used to detect the content of AST and ALT,and the ratio of AST/ALT was calculated.Compared the expression level of tumor markers in each group,and the receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic efficacy of individual and combined application of each index in the diagnosis of primary liver cancer.Results The sera levels of PIVKA-Ⅱ,AFP and AST/ALT ratio in primary liver cancer with HBV infection group were all higher than those in control group(P<0.01).ROC curve analysis showed that with the critical value of PIVKA-Ⅱ,AFP and AST/ALT ratio in serum were 100.42 mAu/mL,232.35 ng/mL and 1.571 in the diagnosis of primary liver cancer with HBV infection,the area under the ROC curve(AUC)were 0.942,0.786 and 0.723 respectively;the sensitivity were 89.70%,58.80%and 51.50%;the specificity were 91.70%,88.10%and 79.80%.The AUC of PIVKA-Ⅱcombined with AST/ALT ratio in the diagnosis of primary liver cancer with HBV infection was 0.955,the sensitivity and specificity wree 86.80%and 93.40%respectively.Conclusion The value of PIVKA-II in the diagnosis of primary liver cancer with HBV infection is obviously better than that of AFP and AST/ALT ratio.The combined detection with AST/ALT ratio will be helpful to improve the diagnostic efficacy of primary liver cancer with HBV infection.
引文
[1] CHEN W,ZHENG R,BAADE P D,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[2] TORRE L A,BRAY F,SIEGEL R L,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[3] CAI S,CAO J,YU T,et al.Effectiveness of entecavir or telbivudine therapy in patients with chronic hepatitis B virus infection pre-treated with interferon compared with de novo therapy with entecavir and telbivudine[J].Medicine(Baltimore),2017,96(22):e7021.
[4] GAO J,SONG P.Combination of triple biomarkers AFP,AFP-L3,and PIVAKII for early detection of hepatocellular carcinoma in China:Expectation[J].Drug Discov Ther,2017,11(3):168-169.
[5] ERTLE J M,HEIDER D,WICHERT M,et al.A combination ofα-fetoprotein and des-γ-carboxy Prothrombin is superior in detection of hepatocellular carcinoma[J].Digestion,2013,87(2):121-131.
[6] ZHANG Y S,CHU J H,CUI S X,et al.Des-γ-carboxy prothrombin(DCP)as a Potential autologous growth factor for the development ofhepatocellular carcinoma[J].Cell Physiol Biochem,2014,34(3):903-915.
[7] HIROKAWA F,HAYASHI M,MIYAMOTO Y,et al.Outcomes and predictors of microvascular invasion of solitary hepatocellular carcinoma[J].Hepatol Res,2014,44(8):846-853.
[8] POTN,CAUCHY F,ALBUQUERQUE M,et al.Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion[J].J Hepatol,2015,62(4):848-854.
[9]王强,陈传艳,王东生,等.血清HE4、CEA、NSE和Cyfra21-1联合检测在肺癌中的诊断价值[J].重庆医学,2017,46(26):3721-3722.
[10]MARRERO J A,SU G L,WEI W,et al.Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients[J].Hepatology,2003,37(5):1114-1121.
[11]KUDO M,IZUMI N,KOKUDO N,et al.Management of hepatocellular carcinoma in Japan:Consensus-Based Clinical PracticeGuidelines proposed by the Japan Society of Hepatology(JSH)2010updeted version[J].Dig Dis,2011,29(3):339-364.
[12]SEO S I,KIM H S,KIM W J,et al.Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma[J].World J Gastroenterol,2015,21(13):3928-3935.
[13]WANG X,ZHANG W,LIU Y,et al.Diagnostic value of prothrombin induced by the absence of vitamin K or antagonist-II(PIVKA-II)for early stage HBV related hepatocellular carcinoma[J].Infect Agent and Cancer,2017,12(1):47.
[14]YU R,TAN Z,XIANG X,et al.Effectiveness of PIVKAII in the detection of hepatocellular carcinoma based on real-worldclinical data[J].BMC Cancer,2017,17(1):608.
[15]COOK N R.Statistical evaluation of prognostic versus diagnosticmodels:Beyond the ROC curve[J].Clin Chem,2008,54(1):17-23.
[2] TORRE L A,BRAY F,SIEGEL R L,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[3] CAI S,CAO J,YU T,et al.Effectiveness of entecavir or telbivudine therapy in patients with chronic hepatitis B virus infection pre-treated with interferon compared with de novo therapy with entecavir and telbivudine[J].Medicine(Baltimore),2017,96(22):e7021.
[4] GAO J,SONG P.Combination of triple biomarkers AFP,AFP-L3,and PIVAKII for early detection of hepatocellular carcinoma in China:Expectation[J].Drug Discov Ther,2017,11(3):168-169.
[5] ERTLE J M,HEIDER D,WICHERT M,et al.A combination ofα-fetoprotein and des-γ-carboxy Prothrombin is superior in detection of hepatocellular carcinoma[J].Digestion,2013,87(2):121-131.
[6] ZHANG Y S,CHU J H,CUI S X,et al.Des-γ-carboxy prothrombin(DCP)as a Potential autologous growth factor for the development ofhepatocellular carcinoma[J].Cell Physiol Biochem,2014,34(3):903-915.
[7] HIROKAWA F,HAYASHI M,MIYAMOTO Y,et al.Outcomes and predictors of microvascular invasion of solitary hepatocellular carcinoma[J].Hepatol Res,2014,44(8):846-853.
[8] POTN,CAUCHY F,ALBUQUERQUE M,et al.Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion[J].J Hepatol,2015,62(4):848-854.
[9]王强,陈传艳,王东生,等.血清HE4、CEA、NSE和Cyfra21-1联合检测在肺癌中的诊断价值[J].重庆医学,2017,46(26):3721-3722.
[10]MARRERO J A,SU G L,WEI W,et al.Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients[J].Hepatology,2003,37(5):1114-1121.
[11]KUDO M,IZUMI N,KOKUDO N,et al.Management of hepatocellular carcinoma in Japan:Consensus-Based Clinical PracticeGuidelines proposed by the Japan Society of Hepatology(JSH)2010updeted version[J].Dig Dis,2011,29(3):339-364.
[12]SEO S I,KIM H S,KIM W J,et al.Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma[J].World J Gastroenterol,2015,21(13):3928-3935.
[13]WANG X,ZHANG W,LIU Y,et al.Diagnostic value of prothrombin induced by the absence of vitamin K or antagonist-II(PIVKA-II)for early stage HBV related hepatocellular carcinoma[J].Infect Agent and Cancer,2017,12(1):47.
[14]YU R,TAN Z,XIANG X,et al.Effectiveness of PIVKAII in the detection of hepatocellular carcinoma based on real-worldclinical data[J].BMC Cancer,2017,17(1):608.
[15]COOK N R.Statistical evaluation of prognostic versus diagnosticmodels:Beyond the ROC curve[J].Clin Chem,2008,54(1):17-23.