O-11 REMODELING OF IMMUNOLOGICAL BIOMARKERS IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH DIRECTACTING ANTIVIRAL THERAPY

Background & Aims

The treatment of hepatitis C with DAAs has offered an 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 in patients upon DAAs treatment.

Methods

50 patients were enrolled before (baseline), during (W2-4 and W8-12 weeks) and post-treatment (W12-24 weeks) with sofosbuvir and daclatasvir ± ribavirin (n=36) or simeprevir (n=14). 15 uninfected blood donors formed the control group (NI). Serum biomarkers CXCL8, CCL11, CCL3, CCL4, CCL2, CCL5, CXCL10, IL-1β, IL-6, TNF-α, IL-12, IFN-γ, IL-15, IL-17, IL1Ra, IL-4, IL-5, IL-9, IL-10, IL-13, FGF-basic, PDGF, VEGF, G-CSF, GM-CSF, IL-7 e IL-2 were quantified by Luminex Bio-Plex Pro™. Mann-Whitney (HCV and NI), Kruskal Wallis (multiple), and Dunn (sequential in pairs) tests compared groups, with significance value if p≤0.05. The study was approved by ethical boards.

Results

At baseline, patients had high levels of chemokines, pro-inflammatory cytokines, and growth factors, with minor increase of regulatory cytokines. The kinetics timeline of baseline fold changes revealed early decline of CXCL8, CCL4, IL6, IL-15, IL-17, IL-9, GM-CSF and IL-7 at W8-12, and late remodeling 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. Baseline ALT ≥69U/L, platelet ≤150,000/mm3 and cirrhosis were related to delayed remodeling in immune response.

Conclusions

The HCV eradication with DAAs results in profound readjustment of the microenvironment of serum immune biomarkers and may be slower in cirrhotic patients. These results add evidence to the knowledge of the process of immune remodeling associated with the rapid viral eradication of HCV with the DAAs.