Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
Clinical Institute, University of Southern Denmark, Odense, Denmark.
Front Cell Infect Microbiol. 2022 Jun 27;12:885824. doi: 10.3389/fcimb.2022.885824. eCollection 2022.
Reducing the treatment duration for chronic hepatitis C could be an important tool in the effort to reach the elimination goals set by the World Health Organization. The current challenge is to predict the target group who will achieve sustained virological response at week 12 (SVR12) with shorter treatment duration. The aim of this exploratory study was to characterize immune subsets with focus on inhibitory receptors in patients who experienced SVR12 or virological relapse following four weeks treatment with glecaprevir/pibrentasvir with or without ribavirin. A total of 32 patients were included in this study of whom 21 achieved SVR12 and 11 had virological relapse. All available samples at baseline (n = 31) and end of treatment (EOT) (n = 30) were processed for flow cytometric analysis in order to measure the expression of PD-1, 2B4, BY55, CTLA-4, TIM-3 and LAG-3 on 12 distinct T cell subsets. At baseline, patients with SVR12 (n=21) had numerically lower frequencies of inhibitory receptors for 83% (60/72) of the investigated T-cell subtypes. The most significant difference observed between the two groups was a lower frequency of stem cell-like memory T-cells CD4PD1 in the SVR group (p = 0.007). Furthermore, we observed a significant positive correlation between baseline viral load and the expression of PD-1 on the total CD8 T-cells and effector memory T-cells CD4 and CD8 for patients with virological relapse. This study suggests a measurable immunologic phenotype at baseline of patients achieving SVR12 after short treatment compared to patients with virological relapse.
缩短慢性丙型肝炎的治疗时间可能是实现世界卫生组织消除目标的重要手段。目前的挑战是预测哪些目标人群在治疗 12 周时(SVR12)能够实现持续病毒学应答(SVR12)。本探索性研究旨在描述实现 SVR12 的患者和治疗 4 周后发生病毒学复发的患者的免疫亚群特征,重点是抑制性受体。共有 32 名患者入组,其中 21 名患者实现了 SVR12,11 名患者发生了病毒学复发。所有基线(n=31)和治疗结束时(EOT)(n=30)的可用样本均进行流式细胞术分析,以测量 12 种不同 T 细胞亚群上 PD-1、2B4、BY55、CTLA-4、TIM-3 和 LAG-3 的表达。基线时,SVR12 患者(n=21)的 83%(60/72)研究 T 细胞亚群的抑制性受体频率数值较低。两组之间最显著的差异是 SVR 组中干细胞样记忆 T 细胞 CD4PD1 的频率较低(p=0.007)。此外,我们观察到病毒载量与治疗后病毒学复发患者的总 CD8 T 细胞和效应记忆 T 细胞 CD4 和 CD8 上 PD-1 的表达呈显著正相关。本研究表明,与病毒学复发患者相比,在接受短时间治疗后实现 SVR12 的患者在基线时具有可测量的免疫表型。