Title:
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Neutrophil and Monocyte Function in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy with Regimens Containing Protease Inhibitors with and without Interferon
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Author:
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Gambato, Martina; Caro Pérez, Noelia; González, Patricia; Cañete, Nuria; Mariño, Zoe; Lens, Sabela; Bonacci, Martín; Bartres, Concepción; Sánchez Tapias, José M. (José María); Carrión, José A.; Forns, Xavier; Juan, Manel; Pérez del Pulgar Gallart, Sofía; Londoño, María Carlota
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Other authors:
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Universitat de Barcelona |
Abstract:
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Real-life data showed an increased incidence of bacterial infections in patients with advanced liver disease receiving a protease inhibitor (PI)-containing antiviral regimen against hepatitis C (HCV). However, the causes of this event are unknown. We hypothesized that PIs might impair innate immune responses through the inhibition of proteases participating in the anti-bacterial functions of neutrophils and monocytes. The aims of the study were to assess phagocytic and oxidative burst capacity in neutrophils and monocytes obtained from patients receiving a PI containing-antiviral regimen, and to determine cytokine secretion after neutrophil stimulation with flagellin. Forty patients with chronic HCV (80% with cirrhosis) were enrolled in the study, 28 received triple therapy (Group A) with pegylated-interferon and ribavirin for 4 weeks followed by the addition of a PI (telaprevir, boceprevir or simeprevir), and 12 patients received an interferon-free regimen (Group B) with simeprevir and sofosbuvir. Phagocytosis and oxidative burst capacity were analyzed by flow cytometry at baseline, week 4, and week 8 of therapy. In neutrophils from Group A patients, oxidative burst rate and oxidative enzymatic activity per cell significantly decreased throughout the study period (p = 0.014 and p = 0.010, respectively). Pairwise comparisons showed a decrease between baseline and week 4 and 8 of therapy. No differences were observed after the introduction of the PI. The oxidative enzymatic activity per cell in monocytes significantly decrease during the study period (p = 0.042) due to a decrease from baseline to week 8 of therapy (p = 0.037) in patients from Group A. None of these findings were observed in Group B patients. Cytokine secretion did not significantly change during the study in both groups. In conclusion, our data suggest that the use interferon (rather than the PI) has a deleterious effect on neutrophil and monocyte phagocytic and oxidative burst capacity in this cohort of patients with HCV-related advanced liver fibrosis. |
Subject(s):
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-Hepatitis C -Malalties cròniques -Interferó -Cirrosi hepàtica -Hepatitis C -Chronic diseases -Interferon -Hepatic cirrhosis |
Rights:
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cc-by (c) Gambato, Martina et al., 2016
http://creativecommons.org/licenses/by/3.0/es |
Document type:
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Article Article - Published version |
Published by:
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Public Library of Science (PLoS)
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