title: Association of serum IFN-λ3 with inflammatory and fibrosis markers in patients with chronic hepatitis C virus infection.
abstract: BACKGROUND
  Hepatitis C virus (HCV) is one of the major causes of liver cancer. The single nucleotide polymorphisms within the IFNL3 gene, which encodes interferon (IFN)-λ(3), are strongly associated with the response to pegylated IFN-α (PEG-IFN-α) plus ribavirin (RBV) therapy in chronic hepatitis C (C-CH) patients. However, the roles of IFN-λ(3) in chronic HCV infection are still elusive. In this study, we aimed to identify clinical and immunological factors influencing IFN-λ(3) and evaluated whether serum IFN-λ(3) levels are involved or not involved in the response to PEG-IFN-α plus RBV therapy.
  
  
  METHODS
  We enrolled 119 C-CH patients with HCV genotype 1 infection who underwent 48 weeks of PEG-IFN-α plus RBV therapy. As controls, 23 healthy subjects and 56 patients with non-HCV viral hepatitis were examined. Serum IFN-λ(3) was quantified by chemiluminescence enzyme immunoassay, and 27 cytokines or chemokines were assayed by the multiplexed BioPlex system.
  
  
  RESULTS
  Serum IFN-λ(3) levels were higher in C-CH patients or acute hepatitis E patients than in healthy volunteers. Such levels did not differ between the IFNL3 genotypes. In C-CH patients, serum IFN-λ(3) was positively correlated with aspartate aminotransferase, alanine aminotransferase, α-fetoprotein, histological activity, fibrosis index, IFN-γ-inducible protein 10, and platelet-derived growth factor. Multivariate analysis showed that IFNL3 single nucleotide polymorphisms, fibrosis score, and macrophage inflammatory protein 1α were involved in the sustained viral clearance in PEG-IFN-α plus RBV therapy; however, serum IFN-λ(3) levels were not involved.
  
  
  CONCLUSIONS
  Serum IFN-λ(3) levels are increased in C-CH patients regardless of the IFNL3 genotype. IFN-λ(3) is a biomarker reflecting the activity and fibrosis of liver disease, but is not correlated with the responsiveness to PEG-IFN-α plus RBV therapy.
authors.affiliation: Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Aoki
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Yoshio
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nomura
authors.forename: Jong-Hon
authors.initials: JH
authors.lastname: Kang
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeda
authors.forename: Shigeko
authors.initials: S
authors.lastname: Naito
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamagiwa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Korenaga
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Imamura
authors.forename: Naohiko
authors.initials: N
authors.lastname: Masaki
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000097:blood* / Q000235:genetics; D008103:Liver Cirrhosis / Q000097:blood* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a