Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Abstract

Background and aimsIncreased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN).MethodssCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls.ResultsAt baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups.Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with high sCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize.ConclusionsThese results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection.

Microbial translocation and T cell activation are modified by direct‐acting antiviral therapy in HCV‐infected patients

“…High levels of surrogate microbial translocation markers in HCV patients confirm the observation by other authors who also suggested that microbial translocation may contribute to persistent inflammation and development of fibrosis in chronic HCV infection . Even if the mechanism underlying the link between HCV infection and microbial translocation was beyond the purpose of our study, a possible explanation could be related to gut epithelial damage, as was observed in a study conducted in HIV/HCV coinfected patients, in whom HIV is known to colonise enterocytes.…”

“…The decrease of sCD14 and LBP levels, although not reaching normal values, persisted 3 months after the end of antiviral treatment. Previous studies on the impact of direct‐acting antivirals on systemic immune activation in HCV patients have reported controversial results; while some studies highlighted a reduction of the markers of immune activation during direct‐acting antiviral treatment, others did not find similar changes …”

Influence of hepatitis C virus eradication with direct‐acting antivirals on the gut microbiota in patients with cirrhosis

“…Our study also confirms that the production of inflammatory cytokines and chemokines is enhanced in patients with chronic HCV infection and is downregulated by viral eradication . Indeed, antiviral therapy significantly improved IL1‐ra, IL2, IL5, FGF‐basic, GM‐CSF, IFN‐gamma, CCL2, CCL3, CCL4, CCL11, CXCL10, PDGF‐BB, and TNF‐alpha plasma levels.…”

“…Indeed, this result may be affected by the relatively short follow-up period, as the evaluation of these parameters was performed 1 year after the end of the DAA treatment, and also by the fact that only patients with well-compen- Our study also confirms that the production of inflammatory cytokines and chemokines is enhanced in patients with chronic HCV infection and is downregulated by viral eradication. [28][29][30][31][32][33][34][35][36][37] Indeed, antiviral therapy significantly improved IL1-ra, IL2, IL5, FGF-basic, , faecal calprotectin) before and 1 y after the end of direct-acting antiviral (DAA) treatment. IL: interleukin; ra:receptor agonist; FGF: fibroblast growth factor; G-CSF: granulocyte colony-stimulating factor; GM-CSF: granulocytemacrophage colony-stimulating factor; IFN: interferon; CCL: C-C motif chemokine ligand; CXCL: C-X-C motif chemokine ligand; PDGF: plateletderived growth factor; TNF: tumour necrosis factor GM-CSF, IFN-gamma, CCL2, CCL3, CCL4, CCL11, CXCL10, PDGF-BB, and TNF-alpha plasma levels.…”

Plasma FABP4 is associated with liver disease recovery during treatment-induced clearance of chronic HCV infection

“…16,17 In our study, only sCD163 remained significantly elevated in patients that received DAA regimen without RBV. This is in accordance with work by Mascia et al showing sustained high levels of sCD163 in DAA-treated CHC patients, 34 and taken together these findings by us and others suggest that residual macrophage activation plays an important role in residual liver disease despite a general dampening of inflammation.…”