Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Leber, B; Balázs, I; Horvath, A; Posch, A; Streit, A; Spindelböck, W; Feldbacher, N; Stiegler, P; Stauber, RE; Rechberger, GN; Kollroser, M; Sattler, W; Nusshold, C; Stadlbauer, V.
Direct acting antiviral therapy rescues neutrophil dysfunction and reduces hemolysis in hepatitis C infection.
Transl Res. 2021; 232:103-114 Doi: 10.1016/j.trsl.2020.12.005 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Balazs Irina
Horvath Angela
Leber Bettina
Co-Autor*innen der Med Uni Graz
Feldbacher Nicole
Kollroser Manfred
Nusshold Christoph
Posch Andreas
Sattler Wolfgang
Spindelböck Walter Johann
Stadlbauer-Köllner Vanessa
Stauber Rudolf
Stiegler Philipp
Streit Andrea

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Chronic hepatitis C virus infection is characterized by multiple extra-hepatic manifestations. Innate immune dysfunction and hemolysis are symptoms which might be associated with each other. We investigated the impact of direct acting antivirals on neutrophil function and its connection to hemolysis. In this prospective study, 85 patients with or without cirrhosis and 21 healthy controls were included. Patients' blood samples were taken at baseline, at the end of therapy and at follow-up 12 weeks after end of therapy. Neutrophil phagocytosis, oxidative burst, and hemolysis parameters were studied. Multivariate analysis was performed to decipher the relationship between hemolysis and neutrophil function. Ex vivo cross-incubation experiments with neutrophils and serum fractions were done. Impaired neutrophil phagocytosis and mild hemolysis were observed in patients with and without cirrhosis. A proteome approach revealed different expression of hemolysis-related serum proteins in patients and controls. Direct acting antiviral therapy restored neutrophil function irrespective of severity of liver disease, achievement of sustained virologic response or type of drug and reduced hemolysis. Treatment with ribavirin delayed the improvement of neutrophil function. Statistical analysis revealed associations of haptoglobin with neutrophil phagocytic capacity. Neutrophil dysfunction could be transferred to healthy cells by incubation with patients' serum fractions (>30 kDa) ex vivo. Neutrophil dysfunction and hemolysis represent extrahepatic manifestations of chronic hepatitis C virus infection and simultaneously improve during direct acting antiviral therapy independently of therapy-related liver function recovery. Therefore, large-scale treatment would not only drive viral eradication but also improve patients' immune system and may reduce susceptibility to infections. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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