Remodeling of immunological biomarkers in patients with chronic hepatitis C treated with direct-acting antiviral therapy

接受直接抗病毒治疗的慢性丙型肝炎患者的免疫生物标志物的重塑

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作者:Isabela Gomes Ribeiro, Jordana Grazziela Alves Coelho-Dos-Reis, Jordana Rodrigues Barbosa Fradico, Ismael Artur da Costa-Rocha, Luciana Diniz Silva, Lucy Ana Dos Santos Fonseca, Rhaissa Carvalho Said Stancioli, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Rosângela Teixeira

Abstract

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/mm3) 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.

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