接受索磷布韦/达拉他韦治疗的慢性丙型肝炎患者血清NOD样受体热蛋白结构域相关蛋白3水平变化及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2025.02.009

摘要/Abstract

摘要： 目的探讨接受索磷布韦/达拉他韦治疗的慢性丙型肝炎(CHC)患者血清NOD样受体热蛋白结构域相关蛋白3(NLRP3)及其下游白细胞介素1β(IL-1β)和IL-18水平变化。方法 2018年3月～2022年3月我院收治的CHC患者104例,均接受索磷布韦/达拉他韦治疗12 w,停药后随访24w。采用ELISA法检测血清NLRP3、IL-1β和IL-18水平。结果治疗前,CHC患者血清NLRP3、IL-1β和IL-18水平分别为(1137.1±172.8)pg/ml、(4.9±1.1)pg/ml和(1027.2±202.1)pg/ml,治疗结束时均显著降低【分别为(713.5±136.7)pg/ml、(2.8±1.0)pg/ml和(644.3±130.8)pg/ml,P＜0.05】;入组时31例低病毒载量组治疗后血清NLRP3、IL-1β和IL-18水平分别为(638.3±122.6)pg/ml、(2.5±0.6)pg/ml和(538.9±111.8)pg/ml,显著低于44例中等病毒载量组【分别为(708.4±130.1)pg/ml、(2.8±0.9)pg/ml和(629.2±123.5)pg/ml,P＜0.05】或29例高病毒载量组【分别为(802.5±137.0)pg/ml、(3.3±0.8)pg/ml和(801.3±140.8)pg/ml,P＜0.05】;在104例CHC患者中,抗病毒治疗获得EVR者74例(71.1%),ETVR者94例(90.4%)和SVR者91例(87.5%);在上述三个时间观察点,病毒学应答患者血清NLRP3、IL-1β和IL-18水平均显著低于未应答患者,差异具有统计学意义(P＜0.05)。结论 CHC患者血清NLRP3及其下游白细胞介素水平异常升高,可能与肝损伤发生和抗病毒治疗不良应答有关,监测血清NLRP3水平变化或有助于预测抗病毒治疗的疗效,值得深入探讨。

关键词: 慢性丙型肝炎, 索磷布韦, 达拉他韦, NOD样受体热蛋白结构域相关蛋白3, 病毒学应答, 治疗

Abstract: Objective The purpose of this study was to investigate the changes and clinical implications of serum NoD-like receptor heat protein domain associated protein 3 (NLRP3), and its downstream interleukin 1β(IL-1β)and IL-18 (IL) levels in patients with chronic hepatitis C (CHC) undergoing sorfosbuvir/daratavir antiviral treatment. Methods 104 patients with CHC were enrolled in to our hospital between March 2018 and March 2022, and all were treated with sorfosbuvir/daratavir for 12 weeks. After discontinuation of the regimen, all patients were followed-up for 24 weeks. Serum NLRP3, IL-1β and IL-18 levels were detected by ELISA. Results At the end of the 12-week antiviral treatment, serum NLRP3,IL-1β and IL-18 levels in 104 patients with CHC were (713.5±136.7)pg/ml,(2.8±1.0)pg/ml and (644.3±130.8)pg/ml, all significantly decreased as compared to [(1137.1±172.8)pg/ml, (4.9±1.1)pg/ml and (1027.2±202.1)pg/ml, respectively, P＜0.05] at presentation; at the end of the 12-week antiviral treatment, serum NLRP3,IL-1β and IL-18 levels in 31 patients with low serum viremia at admission were(638.3±122.6)pg/ml, (2.5±0.6)pg/ml and (538.9±111.8)pg/ml, significantly lower than [(708.4±130.1)pg/ml, (2.8±0.9)pg/ml and (629.2±123.5)pg/ml, respectively, P＜0.05] in 44 patients with moderate serum viremia or [(802.5±137.0)pg/ml, (3.3±0.8)pg/ml and (801.3±140.8)pg/ml, respectively, P＜0.05] in 29 patients with high serum viremia; in our series, the early virologic response (VR) rate, end treatment of virologic response rate and sustained virologic response rate were 71.1%, 90.4% and 87.5%, after antiviral treatment, and serum NLRP3, IL-1β and IL-18 levels in patients with VR at any observation time were all significantly lower than in those without VR (P＜0.05). Conclusion The abnormal elevation of serum NLRP3 and its downstream cytokine levels in patients with CHC might be related to the hepatic pathogenesis and response to antiviral therapy, and we recommend to monitorthe changes of them during antiviral treatment, which might be helpful to predict the antiviral efficacy.

Key words: Hepatitis C, Sofobuvir, Daratavir, Nod-like receptor heat protein domain associated protein 3, Virologic response, Therapy

祁婧, 赵小婷, 王婷婷, 高瑞. 接受索磷布韦/达拉他韦治疗的慢性丙型肝炎患者血清NOD样受体热蛋白结构域相关蛋白3水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2025, 28(2): 194-197.

Qi Jing, Zhao Xiaoting, Wang Tingting, et al. Serum NoD-like receptor heat protein domain associated protein 3 level changes in patients with chronic hepatitis C undergoing sorphobuvir/dallatavir therapy[J]. Journal of Practical Hepatology, 2025, 28(2): 194-197.

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接受索磷布韦/达拉他韦治疗的慢性丙型肝炎患者血清NOD样受体热蛋白结构域相关蛋白3水平变化及其临床意义探讨^*

Serum NoD-like receptor heat protein domain associated protein 3 level changes in patients with chronic hepatitis C undergoing sorphobuvir/dallatavir therapy

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