Neutrophil and monocyte function in patients with chronic hepatitis c undergoing antiviral therapy with regimens containing protease inhibitors with and without interferon
Gambato, Martina (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Caro-Pérez, Noelia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
González, Patricia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Cañete Hidalgo, Nuria (Institut Hospital del Mar d'Investigacions Mèdiques)
Mariño, Zoe (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Lens, Sabela (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Bonacci, Martín (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Bartres, Concepció (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Sánchez-Tapias, José María (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Carrión Rodríguez, José Antonio (Institut Hospital del Mar d'Investigacions Mèdiques)
Forns, Xavier (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Juan, Manuel (Hospital Clínic i Provincial de Barcelona)
Pérez-Del-Pulgar, Sofía (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Londoño, María Carlota (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Universitat Autònoma de Barcelona

Date:	2016
Abstract:	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 HCVrelated advanced liver fibrosis.
Grants:	Ministerio de Economía y Competitividad PI13-00155 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR605
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 11 Núm. 11 (november 2016) , p. e0166631, ISSN 1932-6203

Erratum: https://ddd.uab.cat/record/249581
DOI: 10.1371/journal.pone.0166631
PMID: 27861593

14 p, 1.5 MB

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