炎症标志物对肝癌合并不同类型门静脉栓子的预测价值

周鹏鸽; 卢高峰; 任笑盈; 张涛

doi:10.3969/j.issn.1001-5256.2021.12.021

炎症标志物对肝癌合并不同类型门静脉栓子的预测价值

DOI: 10.3969/j.issn.1001-5256.2021.12.021

郑州大学第二附属医院消化内科，郑州 450014

基金项目:

河南省基础与前沿技术研究计划项目 (162300410128);

科技创新人才培育基金拔尖人才项目 (2020BJRCB01)

详细信息

通信作者:
卢高峰，lugaofeng78@163.com

中图分类号: R735.7
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出版历程
- 收稿日期: 2021-05-11
- 录用日期: 2021-06-02
- 出版日期: 2021-12-20

Value of the inflammatory markers albumin, C-reactive protein, erythrocyte sedimentation rate, and interleukin-6 in predicting hepatocellular carcinoma with different types of portal vein thrombosis

Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China

Research funding:

Basic and Frontier Technology Research Program of Henan Province (162300410128);

Top Talent Project of Scientific and Technological Innovation Talent Training Fund (2020BJRCB01)

摘要

摘要: 目的比较肝癌合并门静脉血栓(PVBT)与肝癌合并门静脉癌栓(PVTT)患者的生化及常规血液指标，探讨炎症指标在不同类型患者中的表达水平及临床意义。方法选取2016年1月—2020年12月于郑州大学第二附属医院诊治的肝癌合并PVBT患者51例(PVBT组)，肝癌合并PVTT患者37例(PVTT组)，随机选取同期住院的肝癌未合并门静脉栓子患者50例作为对照组。收集比较3组患者的一般临床资料、实验室检查结果等。计数资料组间比较采用χ²检验或Kruskal-Wallis秩和检验; 符合正态分布的计量资料组间比较采用单因素方差分析; 非正态分布的计量资料组间比较采用Kruskal-Wallis秩和检验。绘制ROC曲线评价Alb、CRP、ESR及IL-6在PVBT组与PVTT组的表达水平，计算ROC曲线下面积(AUC)，分析各项指标对不同类型栓子的预测价值。结果 3组一般资料及常规生化指标检查结果差异均无统计学意义(P值均＞0.05)，而炎症指标Alb、CRP、血沉(ESR)及IL-6在3组间差异均有统计学意义(H值分别为10.207、24.465、8.917、37.584，P值分别为0.006、＜0.001、0.012、＜0.001)，进一步两组间比较提示，PVTT组Alb水平显著低于PVBT组与对照组，CRP、ESR及IL-6水平显著高于PVBT组与对照组，PVBT组CRP、IL-6水平显著高于对照组(P值均＜0.05)。ROC曲线提示PVTT组Alb、CRP、ESR及IL-6的AUC分别为0.659、0.826、0.679、0.873，PVBT组AUC分别为0.508、0.635、0.503、0.701。结论在肝癌伴PVTT患者中炎症指标IL-6、CRP、ESR高表达，Alb低表达，且预测价值依次递减; 而在肝癌伴PVBT患者中IL-6、CRP、ESR表达相对较低，Alb表达较高，其中IL-6、CRP对PVBT有一定的预测价值，ESR、Alb的预测价值不高。
- 癌，肝细胞 /
- 静脉血栓栓塞 /
- 炎症标志物
Abstract: Objective To investigate the biochemical and routine blood parameters in hepatocellular carcinoma (HCC) patients with portal vein blood thrombus (PVBT) or portal vein tumor thrombosis (PVTT), as well as the expression level and clinical significance of inflammatory indices in patients with different types of PVBT. Methods A total of 51 HCC patients with PVBT and 37 HCC patients with PVTT who were diagnosed and treated in The Second Affiliated Hospital of Zhengzhou University from January 2016 to December 2020 were enrolled as PVBT group and PVTT group, respectively, and 50 HCC patients without portal vein thrombosis who were hospitalized during the same period of time were enrolled as control group. General clinical data and laboratory test results were collected from the three groups. The chi-square test or the Kruskal-Wallis rank sum test was used for comparison of categorical data between groups; a one-way analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis rank sum test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to investigate the expression levels of albumin (Alb), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and interleukin-6 (IL-6) in the PVBT group and the PVTT group, and the area under the ROC curve (AUC) was calculated to analyze their value in predicting different types of thrombosis. Results There were no significant differences in general data and conventional biochemical parameters between the three groups (all P > 0.05), while there were significant differences in the inflammatory indices Alb, CRP, ESR, and IL-6 between the three groups (H=10.207, 24.465, 8.917, and 37.584, P=0.006, P < 0.001, P=0.012, and P < 0.001), and further analysis between two groups showed that the PVTT group had a significantly lower level of Alb and significantly higher levels of CRP, ESR, and IL-6 than the PVBT group and the control group, and the PVBT group had significantly higher levels of CRP and IL-6 than the control group (all P < 0.05). The ROC curve analysis showed that Alb, CRP, ESR, and IL-6 had an AUC of 0.659, 0.826, 0.679, and 0.873, respectively, in the PVTT group, as well as an AUC of 0.508, 0.635, 0.503, and 0.701, respectively, in the PVBT group. Conclusion HCC patients with PVTT tend to have high expression levels of the inflammatory indices IL-6, CRP, and ESR and a low expression level of Alb, and their predictive value decreases successively, while HCC patients with PVBT tend to have relatively low expression levels IL-6, CRP, and ESR and a relatively high expression level of Alb. IL-6 and CRP have a certain value in predicting PVBT, while ESR and ALB have little predictive value.
- Carcinoma, Hepatocellular /
- Venous Thromboembolism /
- Inflammatory Markers

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图 1 Alb、CRP、ESR和IL-6预测不同类型门静脉栓子的ROC曲线

注：由于Alb为负相关指标，故对其取倒数处理。

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表 1 3组患者一般资料比较

指标	PVBT组(n=51)	PVTT组(n=37)	对照组(n=50)	统计值	P值
男[例(%)]	32(62.7)	24(64.9)	30(60.0)	χ²=0.221	0.896
年龄(岁)	61.06±11.53	62.68±10.62	61.20±10.87	F=0.267	0.766
病因[例(%)]				χ²=0.323	0.851
病毒性	39(76.5)	30(81.1)	40(80.0)
非病毒性	12(23.5)	7(18.9)	10(20.0)
Child-Pugh分级[例(%)]				H=0.708	0.702
A级	24(47.1)	18(48.6)	27(54.0)
B级	16(31.4)	11(29.7)	15(30.0)
C级	11(21.6)	8(21.6)	8(16.0)

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表 2 3组实验室检查结果比较

指标	PVBT组(n=51)	PVTT组(n=37)	对照组(n=50)	统计值	P值
ALT(U/L)	56 (38~69)	49(35~72)	39(20~68)	H=5.518	0.063
AST(U/L)	82(60~98)	83(68~93)	84(52~94)	H=0.532	0.767
Alb(g/L)	33.2(31.0~36.0)	30.7(28.6~33.3)¹⁾	34.9(29.7~38.3)²⁾	H=10.207	0.006
TBil(μmol/L)	27.3(17.6~38.5)	26.4(16.9~36.8)	25.5(16.8~32.1)	H=0.429	0.807
RBC(10¹²/L)	2.95(2.24~3.38)	3.13(2.42~3.64)	3.23(2.58~3.67)	H=3.904	0.142
PLT(10⁹/L)	89(74~103)	94(84~109)	106(77~149)	H=4.500	0.105
WBC(10⁹/L)	6.63(3.89~8.88)	7.16(4.93~9.16)	7.47(4.01~8.96)	H=1.012	0.603
NE%	71.0(64.0~83.6)	73.4(63.8~81.5)	67.9(59.5~80.6)	H=1.085	0.581
LY%	21.0(10.7~27.2)	20.0(12.5~28.5)	21.3(11.8~33.2)	H=1.648	0.439
MO%	6.02±2.46	5.76±2.41	5.55±2.13	F=0.267	0.604
CRP(mg/L)	10.30(6.30~27.47)	22.80(12.67~33.52)¹⁾	8.31(6.15~13.20)¹⁾²⁾	H=24.465	＜0.001
ESR(mm/h)	22(15~36)	31(24~49)¹⁾	22(17~30)²⁾	H=8.917	0.012
IL-6(pg/ml)	7.61(4.64~14.88)	15.60(7.22~25.51)¹⁾	4.28(2.81~7.06)¹⁾²⁾	H=37.584	＜0.001
注：与PVBT组比较，1)P＜0.05;与PVTT组比较，2)P＜0.05。

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参考文献(28)

[1]	JANSSEN HL. Changing perspectives in portal vein thrombosis[J]. Scand J Gastroenterol Suppl, 2000, 232: 69-73. http://europepmc.org/abstract/med/11232496
[2]	VIOLI F, CORAZZA GR, CALDWELL SH, et al. Portal vein thrombosis relevance on liver cirrhosis: Italian venous thrombotic events registry[J]. Intern Emerg Med, 2016, 11(8): 1059-1066. DOI: 10.1007/s11739-016-1416-8.
[3]	VILLA E, CAMMÀ C, MARIETTA M, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis[J]. Gastroenterology, 2012, 143(5): 1253-1260. e4. DOI: 10.1053/j.gastro.2012.07.018.
[4]	VIOLI F, FERRO D. Clotting activation and hyperfibrinolysis in cirrhosis: Implication for bleeding and thrombosis[J]. Semin Thromb Hemost, 2013, 39(4): 426-433. DOI: 10.1055/s-0033-1334144.
[5]	VIOLI F. Should the term coagulopathy in cirrhosis be abandoned?[J]. JAMA Intern Med, 2015, 175(5): 862-863. DOI: 10.1001/jamainternmed.2015.90.
[6]	WANG JT, ZHAO HY, LIU YL. Portal vein thrombosis[J]. Hepatobiliary Pancreat Dis Int, 2005, 4(4): 515-518.
[7]	ZHANG ZM, LAI EC, ZHANG C, et al. The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus[J]. Int J Surg, 2015, 20: 8-16. DOI: 10.1016/j.ijsu.2015.05.009.
[8]	AKKIZ H, CARR BI, BAG HG, et al. Serum levels of inflammatory markers CRP, ESR and albumin in relation to survival for patients with hepatocellular carcinoma[J]. Int J Clin Pract, 2021, 75(2): e13593. DOI: 10.1111/ijcp.13593.
[9]	European Association for the Study of the Liver. EASL clinical practice guidelines: Management of hepatocellular carcinoma[J]. J Hepatol, 2018, 69(1): 182-236. DOI: 10.1016/j.jhep.2018.03.019.
[10]	Hepatobiliary Disease Study Group, Chinese Society of Gastroenterology, Chinese Medical Association. Consensus for management of portal vein thrombosis in liver cirrhosis(2020, Shanghai)[J]. J Clin Hepatol, 2020, 36(12): 2667-2674. DOI: 10.3969/j.issn.1001-5256.2020.12.007. 中华医学会消化病学分会肝胆疾病学组. 肝硬化门静脉血栓管理专家共识(2020年, 上海)[J]. 临床肝胆病杂志, 2020, 36(12): 2667-2674. DOI: 10.3969/j.issn.1001-5256.2020.12.007.
[11]	NORTHUP PG, GARCIA-PAGAN JC, GARCIA-TSAO G, et al. Vascular liver disorders, portal vein thrombosis, and procedural bleeding in patients with liver disease: 2020 practice guidance by the American Association for the Study of Liver Diseases[J]. Hepatology, 2021, 73(1): 366-413. DOI: 10.1002/hep.31646.
[12]	LAURSEN I, BRIAND P, LYKKESFELDT AE. Serum albumin as a modulator on growth of the human breast cancer cell line, MCF-7[J]. Anticancer Res, 1990, 10(2A): 343-351. http://www.tandfonline.com/servlet/linkout?suffix=CIT0004&dbid=8&doi=10.1080%2F07357900701407947&key=2346307
[13]	BAǦ_IRSAKÇ_I E, ŞAHIN E, ATABEY N, et al. Role of albumin in growth inhibition in hepatocellular carcinoma[J]. Oncology, 2017, 93(2): 136-142. DOI: 10.1159/000471807.
[14]	JOHNSON C, HAN Y, HUGHART N, et al. Interleukin-6 and its receptor, key players in hepatobiliary inflammation and cancer[J]. Transl Gastrointest Cancer, 2012, 1(1): 58-70. DOI: 10.3978/j.issn.2224-4778.2011.11.02.
[15]	JANG JW, OH BS, KWON JH, et al. Serum interleukin-6 and C-reactive protein as a prognostic indicator in hepatocellular carcinoma[J]. Cytokine, 2012, 60(3): 686-693. DOI: 10.1016/j.cyto.2012.07.017.
[16]	GRIVENNIKOV SI, GRETEN FR, KARIN M. Immunity, inflammation, and cancer[J]. Cell, 2010, 140(6): 883-899. DOI: 10.1016/j.cell.2010.01.025.
[17]	BUDHU A, WANG XW. The role of cytokines in hepatocellular carcinoma[J]. J Leukoc Biol, 2006, 80(6): 1197-1213. DOI: 10.1189/jlb.0506297.
[18]	KARIN M, GRETEN FR. NF-kappaB: Linking inflammation and immunity to cancer development and progression[J]. Nat Rev Immunol, 2005, 5(10): 749-759. DOI: 10.1038/nri1703.
[19]	HE G, KARIN M. NF-κB and STAT3-key players in liver inflammation and cancer[J]. Cell Res, 2011, 21(1): 159-168. DOI: 10.1038/cr.2010.183.
[20]	HUANG X, FAN X, ZHANG R, et al. Systemic inflammation and portal vein thrombosis in cirrhotic patients with gastroesophageal varices[J]. Eur J Gastroenterol Hepatol, 2020, 32(3): 401-405. DOI: 10.1097/MEG.0000000000001526.
[21]	CASTELL JV, GÓMEZ-LECHÓN MJ, DAVID M, et al. Acute-phase response of human hepatocytes: Regulation of acute-phase protein synthesis by interleukin-6[J]. Hepatology, 1990, 12(5): 1179-1186. DOI: 10.1002/hep.1840120517.
[22]	MCKEOWN DJ, BROWN DJ, KELLY A, et al. The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer[J]. Br J Cancer, 2004, 91(12): 1993-1995. DOI: 10.1038/sj.bjc.6602248.
[23]	GALLAND L. Diet and inflammation[J]. Nutr Clin Pract, 2010, 25(6): 634-640. DOI: 10.1177/0884533610385703.
[24]	BELL S, MEHTA G, MOORE K, et al. Ten-year alcohol consumption typologies and trajectories of C-reactive protein, interleukin-6 and interleukin-1 receptor antagonist over the following 12 years: A prospective cohort study[J]. J Intern Med, 2017, 281(1): 75-85. DOI: 10.1111/joim.12544.
[25]	CARR BI, AKKIZ H, GUERRA V, et al. C-reactive protein and hepatocellular carcinoma: Analysis of its relationships to tumor factors[J]. Clin Pract (Lond), 2018, 15(Spec Issue): 625-634. DOI: 10.4172/clinical-practice.1000409.
[26]	BATLIVALA SP. Focus on diagnosis: The erythrocyte sedimentation rate and the C-reactive protein test[J]. Pediatr Rev, 2009, 30(2): 72-74. DOI: 10.1542/pir.30-2-72.
[27]	PINATO DJ, NORTH BV, SHARMA R. A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: The prognostic nutritional index (PNI)[J]. Br J Cancer, 2012, 106(8): 1439-1445. DOI: 10.1038/bjc.2012.92.
[28]	LI X, CHEN ZH, XING YF, et al. Platelet-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma[J]. Tumour Biol, 2015, 36(4): 2263-2269. DOI: 10.1007/s13277-014-2833-9.