title: Longitudinal analysis of peripheral and intrahepatic NK cells in chronic HCV patients during antiviral therapy.
abstract: BACKGROUND
  A strong immune response is integral to the clearance of HCV infection. NK cells are specialized cells that are able to inhibit replication of HCV in infected hepatocytes. Previous studies have correlated therapy outcome in HCV to the expression of various markers on NK cells. However, the effect of viral load reduction on NK cell function during therapy is still largely unknown, particularly in the liver. Therefore we investigated NK cell phenotype and effector function in both the peripheral and intrahepatic compartments during the course of antiviral therapy in chronic HCV patients.
  
  
  METHODS
  Chronic HCV patients were treated for 24 or 48weeks with triple therapy consisting of telaprevir, pegIFN-α and ribavirin. Blood and fine needle aspiration (FNA) biopsies of the liver were collected at start and 6h, 1week and 12weeks during therapy. Flowcytometry was performed for expression of different markers (NKG2A, NKG2D, NKp46, and CD69).
  
  
  RESULTS
  Our results demonstrate a highly activated phenotype of NK cells in liver compared to blood in chronic HCV patients. Six hours after start of triple therapy, no activation of intrahepatic NK cells was observed in the liver as compared to baseline. At 1week after start of triple therapy, the frequency of NK cells with the activating receptor NKp46 was increased in blood, whereas at week 12, the frequencies of the inhibitory receptor NKG2A was increased. No alterations were observed during therapy in liver NK cell phenotype.
  
  
  CONCLUSIONS
  IFN-based therapy for chronic HCV affects NK cell phenotype in peripheral blood more than in the liver.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands.
authors.forename: Michelle
authors.initials: M
authors.lastname: Spaan
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands.
authors.forename: Gertine W
authors.initials: GW
authors.lastname: van Oord
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands; Liver Clinic University Health Network, Division of Gastroenterology, University of Toronto, Canada.
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands. Electronic address: p.a.boonstra@erasmusmc.nl.
authors.forename: Andre
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001769:Blood / Q000276:immunology*; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008137:Longitudinal Studies; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012254:Ribavirin; C486464:telaprevir
keywords: IFN-based therapy; Intrahepatic; NK cells; NKG2A; NKp46; Viral hepatitis