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

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.

The impact of cirrhosis on the inflammatory milieu before and long-term after hepatitis C virus elimination by direct-acting antiviral therapy

“…Nevertheless, our data are consistent with recent studies focusing on non-cirrhotic chronic HCV patients that demonstrated decreased ISG expression after viral elimination 30 . On the other hand, other previous studies suggested that cytokine alterations may still persist in all chronic HCV patients 31 . However, in addition to fibrosis and cirrhosis, other factors may also influence the regeneration of the inflammatory milieu after HCV elimination.…”

Distinct Expression Patterns of Genes Coding for Biological Response Modifiers Involved in Inflammatory Responses and Development of Fibrosis in Chronic Hepatitis C: Upregulation of SMAD-6 and MMP-8 and Downregulation of CAV-1, CTGF, CEBPB, PLG, TIMP-3, MMP-1, ITGA-1, ITGA-2 and LOX

“…Furthermore, gene expression levels were measured in peripheral blood samples, implying that extrapolation of our results to liver tissue should be done with caution. However, different studies suggest that the immunomodulatory effects of CHC infection are detectable on the systemic level, especially in the case of CHC patients without other underlying conditions [24,33,34]. Finally, there was a significant difference in sex distribution between the patient and healthy control groups, with all healthy controls being female.…”

Injecting drug use and hepatitis C virus infection independently increase biomarkers of inflammatory disease risk which are incompletely restored by curative direct-acting antiviral therapy

“…Chronic HCV infection is associated with systemic immune activation and elevated levels of interferons, inflammatory biomarkers including IL-6 and TNF/TNF receptors, chemokines such as CXCL10 and markers of myeloid cell activation including soluble (s) markers sCD163 and sCD14 ( 8 – 13 ). Conflicting data exist regarding the impact of HCV elimination on reversal of immune activation; whilst some biomarkers including CXCL10, IL-10 and sCD163 are consistently reduced following HCV elimination ( 8 , 9 , 13 – 18 ), others including IL-6, TNF and sCD14 are unaffected or inconsistently altered by DAA therapy ( 9 , 13 – 16 ). Importantly, numerous studies suggest that DAA therapy does not restore levels of many parameters including sCD163 and CXCL10 to those found in comparable, HCV-seronegative populations ( 8 , 13 , 14 , 17 – 19 ).…”