基于索磷布韦的直接抗病毒药物对慢性丙型肝炎细胞因子动态变化的影响

摘要/Abstract

摘要： 目的分析基于索磷布韦的直接抗病毒药物(DAAs)对慢性丙型肝炎(CHC)细胞因子动态变化的影响。方法选取2018年6月至2021年10月于淮安市第四人民医院首诊并接受系统治疗的初治CHC患者78例,其中男41例、女37例,年龄(52.3±10.7)岁。根据HCV感染疾病不同阶段分为慢性肝炎、肝硬化,同时选取同期体检者50例作为对照,其中男29例、女21例,年龄(51.2±11.5)岁。CHC诊断符合要求。比较DAAs治疗前后CHC及其不同疾病阶段病例的细胞水平动态变化。结果比较CHC、健康体检者基线资料,健康体检者ALT、AST及TBil分别为20(12,35)U/L、22(14,31)U/L及10.6(8.0,13.6)μmol/L,均显著低于CHC[59(37,92)U/L、47(40,82)U/L及21.8(14.8,38.0)μmol/L],差异具有统计学意义(P<0.05);健康体检者IL-6、单核细胞趋化蛋白-4(MCP-4)及血管内皮生长因子-A(VEGF-A)分别为170.8(122.0,268.9)pg/mL、60.3(39.4,110.5)pg/mL及8.1(3.6,15.9)pg/mL,均显著低于CHC[271.2(184.6,431.2)pg/mL、132.4(96.2,210.5)pg/mL及20.8(12.3,25.8)pg/mL],差异具有统计学意义(P<0.05);健康体检者、CHC患者IL-7为18.0(7.2,25.2)pg/mL、9.2(6.2,14.5)pg/mL,差异具有统计学意义(P<0.05)。基于索磷布韦的DAAs方案治疗12周后,CHC患者持续病毒学应答(SVR)率为93.6%(73/78),其中慢性肝炎病例为98.1%(52/53),肝硬化病例为84.0%(21/25),差异具有统计学意义(P<0.05)。比较治疗前后细胞因子动态变化,治疗前CHC、治疗后慢性肝炎及肝硬化IL-6为271.2(184.6,431.2)pg/mL、202.6(146.2,286.8)pg/mL及238.1(158.7,365.0)pg/mL,差异具有统计学意义(P<0.05);治疗前CHC、治疗后慢性肝炎及肝硬化IL-7为9.2(6.2,14.5)pg/mL、14.5(12.7,19.2)pg/mL及11.6(10.6,13.0)pg/mL,差异具有统计学意义(P<0.05);治疗前CHC、治疗后慢性肝炎及肝硬化MCP-4分别为132.4(96.2,210.5)pg/mL、94.0(68.7,120.9)pg/mL及110.2(98.6,146.5)pg/mL,差异具有统计学意义(P<0.05);治疗后慢性肝炎[25.6(21.1,30.7)pg/mL]、肝硬化[27.0(24.5,32.6)pg/mL]VEGF-A显著高于治疗前CHC[20.8(12.3,25.8)pg/mL,P<0.05],但治疗后慢性肝炎、肝硬化VEGF-A差异不具有统计学意义(P>0.05)。结论 IL-6、IL-7、MCP-4及VEGF-A参与CHC患者免疫炎症反应,基于索磷布韦的DAAs治疗方案能够显著影响上述细胞因子血清浓度,改善患者炎症状态。

关键词: 慢性丙型肝炎, 细胞因子, 直接抗病毒药物, 持续病毒学应答

Abstract: Objective To analyze the effect of direct acting antiviral (DAA) treatment based on sofosbuvir on the dynamic changes of cytokines in chronic hepatitis C (CHC) patients.Methods From June 2018 to October 2021, 78 newly diagnosed CHC patients were selected, including 41 males and 37 females, aged (52.3±10.7) years. According to the different stages of HCV infection, they were divided into a chronic hepatitis group and a cirrhosis group. In addition, 50 physical examination subjects in the same time period were selected as control, including 29 males and 21 females, aged (51.2±11.5) years. The dynamic changes of cytokines levels of CHC at different disease stages were compared before and after DAAs treatment.Results Comparing the baseline data of CHC and healthy people, the ALT, AST and TBil of healthy people were 20 (12, 35) U/L, 22 (14, 31) U/L and 10.6 (8.0, 13.6) ?mol/L, respectively, which were significantly lower than those of [59 (37,92) U/L, 47 (40, 82) U/L and 21.8 (14.8, 38.0) μmol/L in CHC patients, respectively, P<0.05]. The levels of IL-6, MCP-4 and VEGF-A in healthy subjects were 170.8 (122.0, 268.9)pg/mL, 60.3 (39.4, 110.5)pg/mL and 8.1 (3.6, 15.9)pg/mL, and in CHC patients were [271.2(184.6, 431.2)pg/mL, 132.4 (96.2, 210.5)pg/mL and 20.8 (12.3, 25.8)pg/mL], respectively, the difference was statistically significant (P<0.05). The levels of IL-7 in healthy persons and patients with CHC were 18.0 (7.2, 25.2)pg/mL and 9.2 (6.2, 14.5)pg/mL, respectively, the difference was statistically significant (P<0.05). After 12 weeks of treatment with DAAs regimen based on sofosbuvir, the sustained virological response (SVR) rate of CHC patients was 93.6% (73/78), including 98.1% (52/53) of chronic hepatitis cases and 84.0% (21/25) of cirrhosis cases, with statistical significance (P<0.05). Comparing the dynamic changes of cytokines before and after treatment, IL-6 expression in CHC before treatment, chronic hepatitis and liver cirrhosis after treatment were 271.2 (184.6, 431.2) pg/mL, 202.6 (146.2, 286.8) pg/mL and 238.1 (158.7, 365.0) pg/mL, respectively, with statistical differences (P<0.05). The levels of IL-7 in CHC before treatment, chronic hepatitis and liver cirrhosis after treatment were 9.2 (6.2, 14.5) pg/mL, 14.5 (12.7, 19.2) pg/mL and 11.6 (10.6, 13.0) pg/mL, respectively, with statistical significance (P<0.05). The MCP-4 levels of CHC before treatment, chronic hepatitis and liver cirrhosis after treatment were 132.4 (96.2, 210.5) pg/mL, 94.0 (68.7, 120.9) pg/mL and 110.2 (98.6, 146.5) pg/mL, respectively, with statistical significance (P<0.05). After treatment, the levels of VEGF-A in chronic hepatitis [25.6 (21.1, 30.7) pg/mL] and liver cirrhosis [27.0 (24.5, 32.6) pg/mL] were significantly higher than those in CHC [20.8 (12.3, 25.8) pg/mL, P<0.05] before treatment.Conclusion IL-6, IL-7, MCP-4 and VEGF-A are involved in the immune response of CHC patients. DAA treatment based on sophorbuvir can significantly affect the serum concentrations of the inflammatory cytokines and improve the inflammatory state of patients.

Key words: Chronic hepatitis C, Cytokines, Direct acting antiviral treatment, Persistent virological response

叶飞翔, 李晶, 刘景瑞, 刘培, 杜云飞. 基于索磷布韦的直接抗病毒药物对慢性丙型肝炎细胞因子动态变化的影响[J]. 肝脏, 2022, 27(11): 1194-1197.

YE Fei-xiang, LI Jing, LIU Jing-rui, LIU Pei, DU Yun-fei. Effect of direct acting antiviral treatment based on sofosbuvir on the dynamic changes of serum cytokines in chronic hepatitis C patients[J]. Chinese Hepatolgy, 2022, 27(11): 1194-1197.

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