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The CCR5 and CXCR3 Pathways in Hepatitis C Virus Liver Transplanted Recipients Treated by a Direct Antiviral Agent Regimen: Informative Kinetics Profiles
Viral Immunology ( IF 1.5 ) Pub Date : 2021-10-12 , DOI: 10.1089/vim.2021.0035
Giuseppe Colucci 1 , Federica Invernizzi 1 , Sara Uceda Renteria 2 , Riccardo Perbellini 1 , Elisabetta Degasperi 1 , Roberta D'Ambrosio 1 , Enrico Galmozzi 1 , Giovanna Lunghi 2 , Enrico Sguazzini 3 , Pietro Lampertico 1, 4 , Maria Francesca Donato 1
Affiliation  

The CC5 and CXC3 chemokines (CK) pathways are involved in the pathogenesis and outcome of several disease states, including chronic hepatitis C (CHC). The kinetics of Regulated upon Activation Normal T cell Expressed and Secreted (RANTES) (CCL5) and IP-10 (CXCL10) during direct-acting antivirals (DAA) treatment was retrospectively analyzed in 18 liver transplant recipients (LT-R) compared with 20 patients with CHC and 49 healthy controls (HC). CK levels were determined at baseline, week 4, end of treatment, 24 weeks post-treatment (sustained virological response [SVR]), and later-on during follow-up (FU), 12 and 24 months post-DAA. At baseline, median RANTES levels were higher in HC than in both LT-R (p > 0.01) and CHC (p > 0.01), whereas IP-10 levels were higher in LT-R and CHC than in HC (p > 0.05 and p = 0.01), respectively. Mean RANTES values increased during DAA therapy to peak at SVR and FU with significantly higher levels than at baseline in LT-R (p < 0.01) and in CHC, but only at FU (p < 0.003). A subsequent return to baseline or lower levels was observed at extended FU. On the contrary, IP-10 values showed a significant decrease from baseline to SVR and FU in both LT-R (p < 0.03) and CHC (p < 0.01). RANTES profiles during the first 4 weeks of DAA treatment showed an increase or decrease from baseline according to baseline RANTES levels. CCR5 genotyping in LT-R showed the presence of 1 homozygous Δ32/Δ32 and 2 heterozygous WT/Δ32 haplotypes with a prevalence of 5.5% and 11.1%, respectively.

中文翻译:

直接抗病毒药物方案治疗丙型肝炎病毒肝移植受体中的 CCR5 和 CXCR3 途径:信息动力学概况

CC5 和 CXC3 趋化因子 (CK) 通路参与多种疾病状态的发病机制和结果,包括慢性丙型肝炎 (CHC)。回顾性分析了 18 名肝移植受者 (LT-R) 与 20 CHC 患者和 49 名健康对照者 (HC)。CK 水平在基线、第 4 周、治疗结束、治疗后 24 周(持续病毒学应答 [SVR])以及随后的随访期间(FU)、DAA 后 12 和 24 个月测定。在基线时,HC 的 RANTES 中位数水平高于 LT-R ( p  > 0.01) 和 CHC ( p > 0.01),而 LT-R 和 CHC 的 IP-10 水平分别高于 HC(p  > 0.05 和p  = 0.01)。DAA 治疗期间平均 RANTES 值增加,在 SVR 和 FU 达到峰值,在 LT-R ( p  < 0.01) 和 CHC中显着高于基线水平,但仅在 FU ( p  < 0.003)。在延长 FU 时观察到随后返回到基线或更低水平。相反,在 LT-R ( p  < 0.03) 和 CHC ( p < 0.01)。根据基线 RANTES 水平,DAA 治疗前 4 周的 RANTES 曲线显示从基线增加或减少。LT-R 中的 CCR5 基因分型显示存在 1 个纯合 Δ32/Δ32 和 2 个杂合 WT/Δ32 单倍型,患病率分别为 5.5% 和 11.1%。
更新日期:2021-10-17
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