血清异常凝血酶原复合物、甲胎蛋白、铁蛋白检测对HBV相关肝细胞癌的辅助诊断意义

文君; 李嘉; 王春妍; 马莹

doi:10.3969/j.issn.1001-5256.2017.09.020

血清异常凝血酶原复合物、甲胎蛋白、铁蛋白检测对HBV相关肝细胞癌的辅助诊断意义

DOI: 10.3969/j.issn.1001-5256.2017.09.020

天津市第二人民医院肝病Ⅱ科

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中图分类号: R512.62;R735.7
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出版历程
- 收稿日期: 2017-03-20
- 出版日期: 2017-09-20

Value of serum PIVKA-Ⅱ, alpha-fetoprotein, and ferritin in assisting the diagnosis of HBV-related hepatocellular carcinoma

Second Department of Hepatology, Tianjin Second People's Hospital

摘要

摘要: 目的探讨血清异常凝血酶原复合物（PIVKA-Ⅱ）、甲胎蛋白（AFP）、铁蛋白（FER）单项及联合检测在HBV相关肝细胞癌（HCC）辅助诊断中的意义。方法收集2016年6月-2017年2月于天津市第二人民医院住院的40例HBV相关HCC、41例乙型肝炎肝硬化、44例慢性乙型肝炎患者及36例健康体检者的血清,并检测PIVKA-Ⅱ、AFP、FER水平,分别分析三者单独及联合检测诊断HBV相关HCC的受试者工作曲线下面积（AUC）、敏感度和特异度。非正态分布的计量资料组间比较采用非参数KruskalWallis H检验,进一步两两比较采用Mann-Whitney U检验。采用二元logistic进行逐步回归分析产生三项指标联合预测概率的新变量pre。结果血清AFP及PIVKA-Ⅱ水平在乙型肝炎肝硬化、慢性乙型肝炎、HBV相关HCC及健康对照组间的差异均具有统计学意义（χ2值分别为51.446、59.613,P值均<0.001）。AFP水平在HBV相关HCC组显著高于乙型肝炎肝硬化组、慢性乙型肝炎组及健康对照组（Z值分别为-4.609、-6.026、-6.031,P值...
- 癌,肝细胞 /
- 铁蛋白质类 /
- 甲胎蛋白类 /
- 异常凝血酶原 /
- 诊断
Abstract: Objective To investigate the value of serum PIVKA-Ⅱ, alpha-fetoprotein ( AFP) , and ferritin ( FER) measured alone or in combination in assisting the diagnosis of HBV-related hepatocellular carcinoma ( HCC) . Methods A total of 40 patients with hepatitis B virus ( HBV) -related HCC, 41 patients with liver cirrhosis after hepatitis B, 44 patients with chronic hepatitis B ( CHB) , and 36 controls who underwent physical examination were enrolled. Their serum samples were collected and the serum levels of PIVKA-Ⅱ, AFP, and FER were measured. The area under the ROC curve ( AUC) , sensitivity, and specificity of PIVKA-Ⅱ, AFP, and FER measured alone or in combination in the diagnosis of HBV-related HCC were analyzed. The non-parametric Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups, and the Mann-Whitney U test was used for further comparison between two groups. A binary logistic stepwise regression analysis was used to determine the new variable pre of predicted probability of combined measurement of these three indices. Results There were significant differences in the serum levels of AFP and PIVKA-Ⅱ between the liver cirrhosis group, CHB group, HBV-related HCC group, and healthy control group ( χ2= 51. 446 and 59. 613, both P < 0. 001) . The HBV-related HCC group had a significantly higher serum level of AFP than the liver cirrhosis group, CHB group, and healthy control group ( Z =-4. 609, -6. 026, and-6. 031, all P < 0. 001) , and the liver cirrhosis group also had a significantly higher serum level of AFP than the healthy control group ( Z =-2. 30, P = 0. 021) . The HBV-related HCC group had a significantly higher serum level of PIVKA-Ⅱ than the liver cirrhosis group, CHB group, and healthy control group ( Z =-6. 080, -6. 595, and-5. 608, all P < 0. 001) , and the CHB group had a significantly higher serum level of PIVKA-Ⅱ than the healthy control group ( Z =-2. 153, P = 0. 031) . The HBV-related HCC group had a significantly higher serum level of FER than the CHB group ( Z =-2. 177, P = 0. 029) . When measured alone, AFP had the highest sensitivity in the diagnosis of HBV-related HCC ( 79. 49%) , and FER had the highest specificity ( 94. 28%) . When any two of these indices were measured, PIVKA-Ⅱ/AFP had the highest sensitivity ( 89. 74%) , and FER + AFP and FER + PIVKA-Ⅱ had a high specificity ( 97. 14%) . FER/AFP/PIVKA had a sensitivity of 92. 31% and the combined measurement of FER, AFP, and PIVKA-Ⅱhad a specificity of 97. 14%. Conclusion Combined measurement of PIVKA-Ⅱ, AFP, and FER can improve the sensitivity and specificity of single measurement. Serum PIVKA-Ⅱ and AFP have a high clinical value in the diagnosis of HCC; single measurement can well assist the diagnosis, and combined measurement does not increase the diagnostic rate.
- carcinoma, hepatocellular /
- ferritins /
- alpha-fetoproteins /
- protein induced by vitamin K absence or antagonist-Ⅱ /
- diagnosis

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参考文献(21)

[1]INAGAKI Y, TANG W, MAKUUCHI M, et al.Clinical and molecular insights into the hepatocellular carcinoma tumour marker des-γ-carboxyprothrombin[J].Liver Int, 2011, 31 (1) :22-35.

[2]KIM SH, MOON DB, KIM WJ, et al.Preoperative prognostic values ofα-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients with hepatocellular carcinoma for living donor liver transplantation[J].Hepatobiliary Surg Nutr, 2016, 5 (6) :461-469.

[3]CUI SX, YU XF, QU XJ.Roles and signaling pathways of des-γ-carboxyprothrombin in the progression of hepatocellular carcinoma[J].Cancer Invest, 2016, 34 (9) :459-464.

[4]WANG H, LI JJ, MA HX, et al.Diagnostic value of serum AFPcombined with AFP-L3 in hepatocellular carcinoma:a Meta-analysis[J].Anhui Med J, 2016, 37 (10) :1211-1214. (in Chinese) 王浩, 李家军, 马怀幸, 等.甲胎蛋白联合甲胎蛋白异质体L3诊断原发性肝癌的Meta分析[J].安徽医学, 2016, 37 (10) :1211-1214.

[5]WANG CY.Clinical significance of serum ferritin measurement in patients with liver cancer[J].Chin J Clin Ration Drug Use, 2015, 8 (18) :69-70. (in Chinese) 王彩艳.肝癌患者血清铁含量检测的临床意义[J].临床合理用药杂志, 2015, 8 (18) :69-70.

[6]Ministry of Health of the People's Republic of China.Diagnosis, management, and treatment of hepatocellular carcinoma (V2011) [J].J Clin Hepatol, 2011, 27 (11) :1141-1159. (in Chinese) 中华人民共和国卫生部.原发性肝癌诊疗规范 (2011年版) [J].临床肝胆病杂志, 2011, 27 (11) :1141-1159.

[7] Chinese Society of Hepatology and Chinese Society of Infectious Diseases Chinese, Medical Association.The guideline of prevention and treatment for chronic hepatitis B:a 2015 update[J].J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学肝病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.

[8]KIM Y, PARK YH, HWANG S, et al.Diagnostic role of blood tumor markers in predicting hepatocellular carcinoma in liver cirrhosis patients undergoing liver transplantation[J].Ann Transplant, 2016, 21 (15) :660-667.

[9]SONG P, TANG Q, FENG X, et al.Biomarkers:evaluation of clinical utility in surveillance and early diagnosis for hepatocellular carcinoma[J].Scand J Clin Lab Invest Suppl, 2016, 245 (10) :70-76.

[10]JI J, WANG H, LI Y, et al.Diagnostic evaluation of des-γ-carboxyprothrombin versusα-fetoprotein for hepatitis B virus-related hepatocellular carcinoma in China:a large-scale, multicenter study[J].PLo S One, 2016, 11 (4) :e153227.

[11]NANASHIMA A, ABO T, TAURA N, et al.NX-PVKA levels before and after hepatectomy of hepatocellular carcinoma as predictors of patient survival:a preliminary evaluation of an improved assay for PIVKA-II[J].Anticancer Res, 2013, 33 (6) :2689-2697.

[12]VIGGIANI V, PALOMBI S, GENNARINI G, et al.Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients[J].Scand J Gastroenterol, 2016, 51 (10) :1257-1262.

[13]SULTANIK P, GINGUARY A, VANDAME J, et al.Diagnostic accuracy of des-gamma-carboxy prothrombin for hepatocellular carcinoma in a French cohort using the Lumipulse G600 analyzer[J].J Viral Hepat, 2017, 24 (1) :80-85.

[14]OYAMA K, KODA M, SUGIHARA T, et al.Rapid and earlyα-fetoprotein and des-γ-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma[J].Mol Clin Oncol, 2015, 3 (3) :655-662.

[15]OGASAWARA N, TAKAHASHI E, MATSUMOTO T, et al.Prolonged survival in a case of chemotherapy-sensitive gastric cancer that produced alpha-fetoprotein and protein induced by vitamin K antagonist-II[J].Case Rep Gastroenterol, 2015, 9 (1) :113-119.

[16]LIU H, ZHAN DA, LUO HX, et al.Predictive value of alpha fetal protein on prognosis of patients with severe hepatitis B[J].Int JVirol, 2016, 23 (3) :181-183. (in Chinese) 刘华, 詹东昂, 罗红霞, 等.甲胎蛋白对重型乙型肝炎患者生存状况的预测效果[J].国际病毒学杂志, 2016, 23 (3) :181-183.

[17]UEDA N, SHIAHA H, FUJIKAWA T, et al.Exon 2 deletion splice variant of gamma-glutamyl carboxylase causes des-gamma-carboxy prothrombin production in hepatocellular carcinoma cell lines[J].Mol Oncol, 2008, 2 (3) :241-249.

[18]QUAN XL, HU YL, DONG AL.The relationship between the indicators of iron metabolism and hepatic injury in patients with liver diseases[J].Beijing Med J, 2012, 34 (3) :169-173. (in Chinese) 全香兰, 胡玉琳, 董爱莲.肝病患者血清铁代谢指标与肝损伤关系的探讨[J].北京医学, 2012, 34 (3) :169-173.

[19]KELL DB, PRETORIUS E.Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells[J].Metallomics, 2014, 6 (4) :748-773.

[20]CUI C, NIU GP.Multi-tumor markers combined detection in diagnosis of primary hepatocellular caicinoma[J].Mod Oncol, 2015, 23 (9) :1262-1265. (in Chinese) 崔灿, 牛国平.肿瘤标记物联合检测对原发性肝癌的诊断价值[J].现代肿瘤医学, 2015, 23 (9) :1262-1265.

[21]XIA HL, FENG ZW, HAO WM.Application of combined measurement of three indices in early diagnosis of primary liver cancer[J].Int J Lab Med, 2016, 37 (17) :2463-2465. (in Chinese) 夏宏林, 冯忠伟, 郝维敏.3项指标联合检测在原发性肝癌早期诊断中的应用[J].国际检验医学杂志, 2016, 37 (17) :2463-2465.

施引文献

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