Caracterização da resposta imune celular em pacientes com hepatite c crônica tratados com antivirais de ação direta

Abstract

Introduction: Hepatitis C is a disease that affects millions of people around the world. The global estimate of infection reaches about 3% of the world's population. With the introduction of Direct Action Antivirals (DAAs) a new era of interferon free appears. DAAs have excellent efficacy and can cure more than 90% of people with hepatitis C infection. However, understanding the interactions between HCV and host intrigues us to seek information regarding immune restoration after interferon free treatment. Objective: To characterize the cellular immune response, cytokine and chemokine profile in patients with chronic hepatitis C treated with DAAs. Material and Method: Peripheral blood samples were collected from patients diagnosed with chronic hepatitis C (HCV +) before and after treatment and from blood donors (CN). Immunophenotyping of cell subpopulations was performed on the innate and adaptive immune response and quantification of serum cytokine and plasma chemokine concentrations by Flow Cytometry. Results: 82 samples of HCV + patients attended by the FMT-HVD Foundation and 50 candidates for blood donors from the HEMOAM Foundation were collected. The mean age was higher in the group of patients than in the control group (p <0.0001). It was observed predominance of males in the control and female group in HCV + patients. The predominant HCV genotype in the studied population was genotype 1, followed by genotypes 3, 2 and 4, and only one patient had coinfection with HCV 1/2 genotypes. It was observed that the majority of HCV + patients presented fibrosis <F2. These patients had elevated serum levels of ALT and AST transaminases. While the levels of platelets (p <0.0001) and total leukocytes (p <0.0001) were decreased when compared to the control group. Patients treated with DAAS presented SVR> 90% regardless of genotype. Patients with hepatitis C had circulating activated monocytes decreased after treatment when compared to the control group. While plasmacytoid and myeloid dendritic cells, NKT and TCD4 + cells were decreased prior to treatment, these populations were increased in the treatment naive group of patients after treatment when compared to control and experienced patients. On the other hand, TCD8 + lymphocytes and B1 lymphocytes were reduced after treatment. NK cells, Tregulatory Lymphocytes and B lymphocytes do not appear to undergo major changes in the studied population. In addition, cytokines IFN-γ, TNF-α, IL-6, IL-10, IL-4 and IL-17A may be observed and remained increased in the patients experienced even after treatment. The chemokines IL-8, MIG and IP-10 were increased before and after treatment in both naive and experienced patients compared to the control group. Conclusion: At the end of this study we can conclude that free interferon treatment is well tolerated and presents a high rate of sustained virological response, the circulating HCV genotypes in Amazonas are 1, 3, 2 and 4, the cellular profile accompanied by the cytokine profile and chemokines do not appear to be fully reversible at 12 weeks after the end of treatment and may be related to the presence of established hepatic disease and the cytokine and chemokine profile may predict putative biomarkers for SVR outreach and may provide subsidies for subsequent evaluations of staging of hepatitis C-related liver disease in patients treated with DAAs.