An effective interferon-gamma-mediated inhibition of hepatitis C virus replication by natural killer cells is associated with spontaneous clearance of acute hepatitis C in human immunodeficiency virus-positive patients

• DOI: 10.1002/hep.26782
• Publication Date: 2014-01-21T18:55:53Z
• Authors: Pavlos Kokordelis; Benjamin Krämer; Christian Körner; Christoph Boesecke; Esther Voigt; Patrick Ingiliz; Andreas Glässner; Marianne Eisenhardt; Franziska Wolter; Dominik Kaczmarek; Hans Dieter Nisch...; Jürgen K. Rockstroh; Ulrich Spengler; Jacob Nattermann
• Keywords: NKG2D

Hepatitis C virus (HCV) coinfection is an increasing health problem in human immunodeficiency virus-positive (HIV+) individuals. However, a considerable proportion of HIV+ patients manage to overcome acute hepatitis (AHC) spontaneously. In the present study, we analyzed role natural killer (NK) cells modulating course AHC patients. Twenty-seven with (self-limited course: n = 10; chronic 17), 12 (CHC), 8 HIV monoinfected individuals, and healthy controls were studied. NK phenotypically by flow cytometry. Interferon-gamma (IFN-γ) secretion, degranulation (CD107a), anti-HCV (= inhibition HCV replication) activity subpopulations using HuH7A2HCVreplicon cell system. frequency did not differ significantly between self-limited AHC. found from self-limiting infection be more effective inhibiting replication vitro than developing CHC. Of note, antiviral showed no significant correlation degranulation, but was positively correlated IFN-γ blocking experiments confirmed important for cell-mediated replication. Accordingly, that spontaneously cleared displayed stronger secretion those infection. Finally, observed high expression NKG2D NKp46, respectively, associated aHCV. these receptors impaired activity. Conclusion: Our data suggest strong IFN-γ-mediated response (Hepatology 2014;59:814–827)