title: Lymphocytes degranulation in liver in hepatitis C virus carriers is associated with IFNL4 polymorphisms and ALT levels.
abstract: BACKGROUND
  The polymorphisms of IFNL4 are strongly associated with both spontaneous hepatitis C virus (HCV) clearance and response to peg-IFN-α/ribavirin treatment. To further establish the biological effects of the IFNL4 and rs1297860 variations, we studied the activity of liver immune cells.
  
  
  METHODS
  Fresh liver samples were collected from HCV-infected patients before any treatment and from NASH patients as controls. Degranulation activity of each lymphocyte type was assessed by the surface expression of CD107a. IFNL4 polymorphisms and HCV genotypes were determined.
  
  
  RESULTS
  In the liver, frequency of CD107a(+) immune cells was significantly higher in HCV patients compared to NASH patients. Higher degranulation activity was observed in lymphocytes of HCV patients with favorable IFNL4 genotypes compared to patients with unfavorable genotypes. Multivariate regression analyses indicated that serum ALT levels were dependent on both Metavir activity score and frequency of CD107a positive NKT cells. The high level of degranulation activity observed before treatment was associated with a high HCV RNA decline at the early stage of peg-IFN-α/ribavirin treatment in patients with favorable genotypes.
  
  
  CONCLUSIONS
  These data underline that intrahepatic lymphocyte degranulation activity in HCV-infected patients is associated with IFNL4 polymorphisms and contributes to the clearance of HCV in patients with favorable genotypes under antiviral therapy.
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jouvin-Marche
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Macek Jílková
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine Pole DiGi-Dune, Centre Hospitalier Universitaire de Grenoble, La Tronche, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Thelu
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine.
authors.forename: Helene
authors.initials: H
authors.lastname: Marche
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine.
authors.forename: Emilie
authors.initials: E
authors.lastname: Fugier
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Van Campenhout
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine.
authors.forename: Xuan Su
authors.initials: XS
authors.lastname: Hoang
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine Pole DiGi-Dune, Centre Hospitalier Universitaire de Grenoble, La Tronche, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Marlu
authors.affiliation: Pole DiGi-Dune, Centre Hospitalier Universitaire de Grenoble, La Tronche, FranceINSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine Pole DiGi-Dune, Centre Hospitalier Universitaire de Grenoble, La Tronche, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sturm
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine.
authors.forename: Mary
authors.initials: M
authors.lastname: Callanan
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine Pole DiGi-Dune, Centre Hospitalier Universitaire de Grenoble, La Tronche, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine Pole DiGi-Dune, Centre Hospitalier Universitaire de Grenoble, La Tronche, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.affiliation: INSERM, U823, Grenoble, France Université Joseph Fourier-Grenoble 1, Faculté de Médecine Pole DiGi-Dune, Centre Hospitalier Universitaire de Grenoble, La Tronche, France.
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Marche
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000494:pharmacology; D015550:Cell Degranulation; D005234:Fatty Liver / Q000188:drug therapy; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000821:virology; D008214:Lymphocytes / Q000166:cytology / Q000821:virology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D012254:Ribavirin / Q000494:pharmacology; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D000998:Antiviral Agents; D016898:Interferon-alpha; D007378:Interleukins; D052118:Lysosomal-Associated Membrane Protein 1; D012367:RNA, Viral; D012254:Ribavirin; C579163:IFNL4 protein, human; D000095022:Interferon Lambda
keywords: ISG; interferon lambda; natural killer cells. T lymphocytes