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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Spindelboeck, W; Horvath, A; Tawdrous, M; Schmerböck, B; Zettel, G; Posch, A; Streit, A; Jurse, P; Lemesch, S; Horn, M; Wuensch, G; Stiegler, P; Stauber, RE; Leber, B; Stadlbauer, V.
Triple Therapy with First Generation Protease Inhibitors for Hepatitis C Markedly Impairs Function of Neutrophil Granulocytes.
PLoS One. 2016; 11(3):e0150299-e0150299 Doi: 10.1371/journal.pone.0150299 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Horvath Angela
Leber Bettina
Spindelböck Walter Johann
Co-Autor*innen der Med Uni Graz
Lemesch Sandra
Stadlbauer-Köllner Vanessa
Stauber Rudolf
Stiegler Philipp
Tawdrous Monika
Wünsch Gerit
Zettel Gabriele

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First-generation HCV protease inhibitors represent a milestone in antiviral therapy for chronic hepatitis C infection (CHC), but substantially increased rates of viral clearance are offset by increased rates of infection and infection-associated deaths, especially of patients with advanced liver disease. We aimed to assess whether first generation protease inhibitors interfere with neutrophil function. We included 108 consecutive, retrospective CHC patients and 44 consecutive, prospective CHC patients who were treated with peginterferon and ribavirin with or without protease inhibitors according to the guidelines in the period of November 2012 to June 2015. 33 healthy volunteers served as controls. Infection data were evaluated in all patients. Neutrophil phagocytosis, oxidative burst, elastase and diamine oxidase levels during 12 weeks of triple (n = 23) or dual therapy (n = 21) were studied in the prospective part. In the retro- and prospective cohorts patients experiencing clinically relevant infections were significantly more frequent during protease inhibitor therapy (31% and 26%) than during therapy with peginterferon and ribavirin (13% and 0%). Neutrophil phagocytosis decreased to 40% of baseline with addition of protease inhibitors to P/R but recovered 6 months after end of treatment. Protease inhibitors also seemed to reduce serum elastase levels but did not impact on gut permeability. Impaired neutrophil function during triple therapy with first generation HCV protease inhibitors may explain the high infection rate associated to these treatments and be of relevance for treatment success and patient survival.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Drug Therapy, Combination -
Female -
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - immunology
Humans -
Interferon-alpha - pharmacology
Interferon-alpha - therapeutic use
Leukocyte Elastase - metabolism
Male -
Middle Aged -
Neutrophils - drug effects
Neutrophils - enzymology
Neutrophils - immunology
Oligopeptides - pharmacology
Oligopeptides - therapeutic use
Proline - analogs & derivatives
Proline - pharmacology
Proline - therapeutic use
Prospective Studies -
Protease Inhibitors - pharmacology
Protease Inhibitors - therapeutic use
Retrospective Studies -
Ribavirin - pharmacology
Ribavirin - therapeutic use
Treatment Outcome -

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