Association of serum IFN-λ3 with inflammatory and fibrosis markers in patients with chronic hepatitis C virus infection

J Gastroenterol. 2015 Aug;50(8):894-902. doi: 10.1007/s00535-014-1023-2. Epub 2014 Dec 14.


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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • Case-Control Studies
  • Drug Therapy, Combination
  • Female
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Inflammation Mediators / blood*
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / blood*
  • Interleukins / genetics
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use


  • Antiviral Agents
  • Biomarkers
  • IFNL3 protein, human
  • Inflammation Mediators
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2a