Pós-graduação em Ciências Aplicadas da Saúde do Adulto, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Hospital Das Clínicas / Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Grupo Integrado de Pesquisa em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz - FIOCRUZ-Minas, Belo Horizonte, MG, Brazil.
Grupo Integrado de Pesquisa em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz - FIOCRUZ-Minas, Belo Horizonte, MG, Brazil; Laboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Antiviral Res. 2021 Jun;190:105073. doi: 10.1016/j.antiviral.2021.105073. Epub 2021 Apr 19.
The HCV treatment with DAAs has offered a unique opportunity to analyze the changes in the immune system caused by the rapid inhibition of viral replication. We sought to analyze the kinetics profiles of serum biomarkers (LuminexTM) in fifty patients with chronic hepatitis C enrolled in a longitudinal investigation carried out before (baseline), during (W2-4 and W8-12 weeks) and post-treatment (W12-24 weeks) with sofosbuvir plus daclatasvir or simeprevir. The results demonstrated a clear biomarker overproduction in HCV patients at baseline. The kinetics timeline of baseline fold changes upon DAAs treatment revealed an early decline of CXCL8, CCL4, IL-6, IL-15, IL-17, IL-9, GM-CSF and IL-7 at W8-12 and a late shift towards lower levels of CCL3, CCL2, CCL5, IL1β, TNF-α, IL-12, IFN-γ, IL1-Ra, IL-4, IL-10, IL-13, PDGF, VEGF, G-CSF at W12-24. Our data demonstrated that HCV treatment with DAAs resulted in a clear change of the serum biomarker overproduction, hallmark of untreated HCV patients. High ALT (>69U/L), low platelet (≤150,000/mm) and cirrhosis status at baseline were factors related to delayed immune response shift, as well as, in the kinetics of baseline fold changes in serum biomarkers. These findings added novel evidences for the immunological restoration process triggered by DAAs.
HCV 的 DAA 治疗为分析病毒快速抑制引起的免疫系统变化提供了独特的机会。我们试图分析在接受索非布韦加达拉他韦或simeprevir 治疗之前（基线）、治疗期间（第 2-4 周和第 8-12 周）和治疗后（第 12-24 周）的五十例慢性丙型肝炎患者的血清生物标志物（LuminexTM）动力学谱。结果表明，HCV 患者基线时明显的生物标志物过度产生。DAAs 治疗基线倍数变化的动力学时间轴显示，第 8-12 周时 CXCL8、CCL4、IL-6、IL-15、IL-17、IL-9、GM-CSF 和 IL-7 早期下降，第 12-24 周时 CCL3、CCL2、CCL5、IL1β、TNF-α、IL-12、IFN-γ、IL1-Ra、IL-4、IL-10、IL-13、PDGF、VEGF、G-CSF 水平较低。我们的数据表明，DAA 治疗 HCV 导致未经治疗的 HCV 患者的血清生物标志物过度产生的明显变化。基线时高 ALT（>69U/L）、血小板低（≤150,000/mm）和肝硬化状态是与免疫反应延迟以及血清生物标志物基线倍数变化动力学相关的因素。这些发现为 DAA 触发的免疫恢复过程提供了新的证据。
