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.