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.
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-CHpatients 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-CHpatients or acute hepatitis Epatients than in healthy volunteers. Such levels did not differ between the IFNL3 genotypes. In C-CHpatients, 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-CHpatients 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: E Teshale; M Lu; L B Rupp; S D Holmberg; A C Moorman; P Spradling; V Vijayadeva; J A Boscarino; M A Schmidt; S C Gordon Journal: J Viral Hepat Date: 2014-08-01 Impact factor: 3.728
Authors: Tobias Marcello; Arash Grakoui; Giovanna Barba-Spaeth; Erica S Machlin; Sergei V Kotenko; Margaret R MacDonald; Charles M Rice Journal: Gastroenterology Date: 2006-10-01 Impact factor: 22.682
Authors: Mohammed Eslam; Duncan McLeod; Kebitsaone Simon Kelaeng; Alessandra Mangia; Thomas Berg; Khaled Thabet; William L Irving; Gregory J Dore; David Sheridan; Henning Grønbæk; Maria Lorena Abate; Rune Hartmann; Elisabetta Bugianesi; Ulrich Spengler; Angela Rojas; David R Booth; Martin Weltman; Lindsay Mollison; Wendy Cheng; Stephen Riordan; Hema Mahajan; Janett Fischer; Jacob Nattermann; Mark W Douglas; Christopher Liddle; Elizabeth Powell; Manuel Romero-Gomez; Jacob George Journal: Nat Genet Date: 2017-04-10 Impact factor: 38.330
Authors: Alicja E Grzegorzewska; Monika K Świderska; Adrianna Mostowska; Paweł P Jagodziński Journal: Biomed Res Int Date: 2017-10-31 Impact factor: 3.411