Influence of sofosbuvir-based antiviral therapy on the expression profile of cytokines and chemokines in patients with chronic hepatitis C
-
摘要: 目的探讨以索磷布韦为基础的抗病毒方案对慢性丙型肝炎患者细胞因子/趋化因子表达谱的影响。方法选取2018年8月-2019年1月于海南省人民医院就诊的慢性丙型肝炎初治患者37例,HCV基因1b型、3型和6型患者接受索磷布韦维帕他韦片治疗,2a型患者接受索磷布韦联合利巴韦林治疗,同时纳入15例健康对照者。采用多细胞因子检测方法对血清中36种细胞因子/趋化因子进行检测。比较慢性丙型肝炎患者和健康对照者基线细胞因子/趋化因子的表达差异,观察治疗12周后慢性丙型肝炎患者细胞因子/趋化因子的变化。符合正态分布的计量资料2组间比较采用t检验,多组间比较采用单因素方差分析,相关性分析采用Pearson相关性检验;不符合正态分布的计量资料2组间比较采用Mann-Whitney U检验或Wilcoxon检验,多组间比较采用Kruskal-Wallis H检验,相关性分析采用Spearman相关性检验。结果慢性丙型肝炎患者血清IL-6、干扰素诱导蛋白(IP) 10、单核细胞趋化蛋白(MCP) 4、巨噬细胞炎症蛋白(MIP) 3α和血管内皮生长因子(VEGF) A水平均明显高于健康对照组,差异均有统计学意义(Z...Abstract: Objective To investigate the influence of sofosbuvir-based antiviral therapy on the expression profile of cytokines and chemokines in patients with chronic hepatitis C. Methods A total of 37 previously untreated patients with chronic hepatitis C who visited Department of Infectious Diseases in Hainan Provincial People's Hospital from August 2018 to January 2019 were enrolled. The patients with HCV genotypes 1 b,3,and 6 were given oral sofosbuvir and velpatasvir tablets,while those with HCV genotype 2 a were given oral sofosbuvir combined with ribavirin. A total of 15 healthy individuals were enrolled as healthy controls. Multiple cytokine assay kits were used to measure the serum levels of 36 cytokines and chemokines. The expression profile of cytokines and chemokines at baseline were compared between chronic hepatitis C patients and healthy controls,and the changes in the expression of cytokines and chemokines were analyzed for chronic hepatitis C patients at 12 weeks of treatment. The t-test was used for comparison of normally distributed continuous data between the two groups,and a one-way analysis of variance was used for comparison between multiple groups,the Pearson correlation analysis was used to investigate correlation; the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups,the Spearman correlation analysis was used to investigate correlation. Results Compared with the healthy control group,the chronic hepatitis C group had significantly higher levels of interleukin-6(IL-6),interferon-inducible protein 10(IP-10),monocyte chemotactic protein-4(MCP-4),macrophage inflammatory protein-3α(MIP-3α),and vascular endothelial growth factor-A(VEGF-A)(Z = 2. 020,2. 368,2. 752,1. 976,and 2. 110,P= 0. 019,0. 049,0. 003,0. 024,and 0. 002) and a significantly lower level of interleukin-7(IL-7)(Z = 2. 778,P = 0. 048). There were no significant differences in the remaining 30 cytokines and chemokines between the healthy controls and the chronic hepatitis C patients(all P > 0. 05). The levels of cytokines and chemokines were not correlated with HCV RNA or alanine aminotransferase(all P > 0. 05). After 12 weeks of sofosbuvir-based antiviral therapy,there were significant reductions in the serum levels of IL-6,IP-10,MCP-4,and MIP-3α(all P < 0. 05),while there were no significant changes in IL-7 and VEGF-A after treatment(both P > 0. 05). Conclusion IL-6,IP-10,MCP-4,MIP-3α,and VEGF-A might be involved in HCV-mediated inflammatory response,and sofosbuvir-based antiviral therapy can effectively reduce the expression of IL-6,IP-10,MCP-4,and MIP-3α and inhibit liver inflammation.
-
Key words:
- hepatitis C,chronic /
- sofosbuvir /
- antiviral agents /
- cytokines /
- chemokine factors
-
[1] LI H,HUANG MH,JIANG JD,et al. Hepatitis C:From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy[J]. World J Gastroenterol,2018,24(47):5297-5311. [2] ZHANG X,LI YG. Current status of the application of directacting antiviral agents in treatment of chronic hepatitis C and existing problems[J]. J Clin Hepatol,2018,34(4):853-857.(in Chinese)张熙,李用国.慢性丙型肝炎直接抗病毒药物应用现状及存在问题[J].临床肝胆病杂志,2018,34(4):853-857. [3] ATRETKHANY KN,DRUTSKAYA MS,NEDOSPASOV SA,et al. Chemokines, cytokines and exosomes help tumors to shape inflammatory microenvironment[J]. Pharmacol Ther,2016,168:98-112. [4] HE D,LI M,GUO S,et al. Expression pattern of serum cytokines in hepatitis B virus infected patients with persistently normal alanine aminotransferase levels[J]. J Clin Immunol,2013,33(7):1240-1249. [5] LIAN JQ,YANG XF,ZHAO RR,et al. Expression profiles of circulating cytokines,chemokines,and immune cells in patients with hepatitis B virus infection[J]. Hepat Mon,2014,14(6):e18992. [6] JABO N'SKA J,PAWOWSKI T,LASKUS T,et al. The correlation between pretreatment cytokine expression patterns in peripheral blood mononuclear cells with chronic hepatitis C outcome[J]. BMC Infect Dis,2015,15:556. [7] ROSE-JOHN S. IL-6 trans-signaling via the soluble IL-6receptor:Importance for the pro-inflammatory activities of IL-6[J]. Int J Bio Sci,2012,8(9):1237-1247. [8] NASEEM S,MANZOOR S,JAVED A,et al. Interleukin-6 rescues lymphocyte from apoptosis and exhaustion induced by chronic hepatitis C virus infection[J]. Viral Immunol,2018,31(9):624-631. [9] NAWAZ R,ZAHID S,IDRESS M,et al. HCV-induced regulatory alterations of IL-1β,IL-6,TNF-α,and IFNγoperative,leading liver en-route to non-alcoholic steatohepatitis[J].Inflamm Res,2017,66(6):477-486. [10] KAO JT,FENG CL,YU CJ,et al. IL-6,through p-STAT3rather than p-STAT1,activates hepatocarcinogenesis and affects survival of hepatocellular carcinoma patients:A cohort study[J]. BMC Gastroenterol,2015,15:50. [11] HOU H,KANG Y,ZENG Y,et al. Interleukin-7 augments CD8+T cells function and promotes viral clearance in chronic hepatitis C virus infection[J]. Cytokine,2018,102:26-33. [12] ZHANG ZH,JIANG BC,LIU XH,et al. Interleukin-7 regulates T follicular helper cell function in patients with chronic hepatitis C[J]. Viral Immunol,2018,31(6):417-425. [13] JUDGE CJ,KOSTADINOVA L,SHERMAN KE,et al. CD56bright NK IL-7Rαexpression negatively associates with HCV level,and IL-7-induced NK function is impaired during HCV and HIV infections[J]. J Leukoc Biol,2017,102(1):171-184. [14] NAJAFI FARD S,SCHIETROMA I,CORANO SCHERI G,et al.Direct-acting antiviral therapy enhances total CD4+and CD8+T-cells responses,but does not alter T-cells activation among HCV mono-infected,and HCV/HIV-1 co-infected patients[J]. Clin Res Hepatol Gastroenterol,2018,42(4):319-329. [15] GREBELY J,FELD JJ,APPLEGATE T,et al. Plasma interferon-gamma-inducible protein-10(IP-10)levels during acute hepatitis C virus infection[J]. Hepatology,2013,57(6):2124-2134. [16] RAU M,SCHMITT J,BERG T,et al. Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+T cells in cholestatic HCV patients[J]. PLo S One,2018,13(12):e0208225. [17] LI J,WANG XF. Liver-targeted expression of chemokine CXCL10 inhibits Con A-induced liver injury[J]. Chin J Immunol,2017,33(6):828-832.(in Chinese)李静,王学富.肝脏靶向表达趋化因子CXCL10抑制Con A诱导的肝脏损伤[J].中国免疫学杂志,2017,33(6):828-832. [18] EL RAZIKY M,ELSHARKAWY A,SAID SE,et al. IP-10 serum level in chronic hepatitis C virus patients:Relation to fibrosis and response to combined interferon/ribavirin therapy[J].J Interferon Cytokine Res,2015,35(8):649-653. [19] OSBURN WO,LEVINE JS,CHATTERGOON MA,et al. Antiinflammatory cytokines,pro-fibrogenic chemokines and persistence of acute HCV infection[J]. J Viral Hepat,2013,20(6):404-413. [20] BENKHEIL M,van HAELE M,ROSKAMS T,et al. CCL20,a direct-acting pro-angiogenic chemokine induced by hepatitis C virus(HCV):Potential role in HCV-related liver cancer[J]. Exp Cell Res,2018,372(2):168-177. [21] MUKOZU T,NAGAI H,MATSUI D,et al. Serum VEGF as a tumor marker in patients with HCV-related liver cirrhosis and hepatocellular carcinoma[J]. Anticancer Res,2013,33(3):1013-1021. [22] VILLANI R,FACCIORUSSO A,BELLANTI F,et al. DAAs rapidly reduce inflammation but increase serum VEGF level:A rationale for tumor risk during anti-HCV treatment[J]. PLo S One,2016,11(12):e0167934.
本文二维码
计量
- 文章访问数: 1289
- HTML全文浏览量: 64
- PDF下载量: 239
- 被引次数: 0