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

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)-lambda(3), are strongly associated with the response to pegylated IFN-alpha (PEG-IFN-alpha) plus ribavirin (RBV) therapy in chronic hepatitis C (C-CH) patients. However, the roles of IFN-lambda(3) in chronic HCV infection are still elusive. In this study, we aimed to identify clinical and immunological factors influencing IFN-lambda(3) and evaluated whether serum IFN-lambda(3) levels are involved or not involved in the response to PEG-IFN-alpha plus RBV therapy. We enrolled 119 C-CH patients with HCV genotype 1 infection who underwent 48 weeks of PEG-IFN-alpha plus RBV therapy. As controls, 23 healthy subjects and 56 patients with non-HCV viral hepatitis were examined. Serum IFN-lambda(3) was quantified by chemiluminescence enzyme immunoassay, and 27 cytokines or chemokines were assayed by the multiplexed BioPlex system. Serum IFN-lambda(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-lambda(3) was positively correlated with aspartate aminotransferase, alanine aminotransferase, alpha-fetoprotein, histological activity, fibrosis index, IFN-gamma-inducible protein 10, and platelet-derived growth factor. Multivariate analysis showed that IFNL3 single nucleotide polymorphisms, fibrosis score, and macrophage inflammatory protein 1 alpha were involved in the sustained viral clearance in PEG-IFN-alpha plus RBV therapy; however, serum IFN-lambda(3) levels were not involved. Serum IFN-lambda(3) levels are increased in C-CH patients regardless of the IFNL3 genotype. IFN-lambda(3) is a biomarker reflecting the activity and fibrosis of liver disease, but is not correlated with the responsiveness to PEG-IFN-alpha plus RBV therapy.