The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C

Author:

Radmanić Leona1ORCID,Bodulić Kristian2ORCID,Šimičić Petra1,Vince Adriana34,Židovec Lepej Snježana1ORCID

Affiliation:

1. Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, Croatia

2. Research Department, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, Croatia

3. Department of Viral Hepatitis, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, Croatia

4. School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

Abstract

In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment.

Funder

Strengthening the capacity of CerVirVac for research in virus immunology and vaccinology

European Regional Development Fund

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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