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以索磷布韦为基础的治疗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
Influence of sofosbuvir-based antiviral therapy on the expression profile of cytokines and chemokines in patients with chronic hepatitis C
文章发布日期:2019年09月05日  来源:  作者:高 艺,梁志军,符 健  点击次数:136次  下载次数:22次

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【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值分别为2.020、2.368、2.752、1.976、2.110,P 值分别为0.019、0.049、0.003、0.024、0.002),而慢性丙型肝炎患者血清IL-7的水平显著低于健康对照组,差异有统计学意义(Z=2.778,P=0.048)。其他30种细胞因子/趋化因子的表达水平在健康对照和慢性丙型肝炎患者中的差异均无统计学意义(P值均>0.05)。细胞因子/趋化因子水平与HCV RNA、ALT水平无明显相关性(P值均>0.05)。在以索磷布韦为基础的抗HCV治疗12周后,慢性丙型肝炎患者血清IL-6、IP-10、MCP-4和MIP-3α的水平均较基线明显降低,差异均有统计学意义(P值均<0.05),而IL-7和VEGF-A的水平在基线和治疗12周时的差异均无统计学意义(P值均>0.05)。结论 IL-6、IP-10、MCP-4、MIP-3α和VEGF-A可能参与了HCV介导的炎症应答,以索磷布韦为基础的有效抗病毒治疗可抑制IL-6、IP-10、MCP-4和MIP-3α表达,抑制肝脏炎症。
【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 1b, 3, and 6 were given oral sofosbuvir and velpatasvir tablets, while those with HCV genotype 2a 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.
【关键字】:丙型肝炎, 慢性; 索非布韦; 抗病毒药; 细胞因子类; 趋化因子类
【Key words】:hepatitis C, chronic; sofosbuvir; antiviral agents; cytokines; chemokine factors
【引证本文】:GAO Y, LIANG ZJ, FU J. Influence of sofosbuvir-based antiviral therapy on the expression profile of cytokines and chemokines in patients with chronic hepatitis C[J]. J Clin Hepatol, 2019, 35(10): 2200-2204. (in Chinese)
高艺, 梁志军, 符健. 以索磷布韦为基础的治疗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[J]. 临床肝胆病杂志, 2019, 35(10): 2200-2204.

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