Association of serum IFN-[lambda]^sub 3^ with inflammatory and fibrosis markers in patients with chronic hepatitis C virus infection

• Published in: Journal of gastroenterology 2015-08, Vol.50 (8), p.894
• Main Authors: Aoki, Yoshihiko, Sugiyama, Masaya, Murata, Kazumoto, Yoshio, Sachiyo, Kurosaki, Masayuki, Hashimoto, Satoru, Yatsuhashi, Hiroshi, Nomura, Hideyuki, Kang, Jong-hon, Takeda, Tsutomu, Naito, Shigeko, Kimura, Tatsuji, Yamagiwa, Yoko, Korenaga, Masaaki, Imamura, Masatoshi, Masaki, Naohiko, Izumi, Namiki, Kage, Masayoshi, Mizokami, Masashi, Kanto, Tatsuya
• Format: Article
• Language: English
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-014-1023-2

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)-[lambda]^sub 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]^sub 3^ in chronic HCV infection are still elusive. In this study, we aimed to identify clinical and immunological factors influencing IFN-[lambda]^sub 3^ and evaluated whether serum IFN-[lambda]^sub 3^ levels are involved or not involved in the response to PEG-IFN-[alpha] plus RBV therapy. Methods 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]^sub 3^ was quantified by chemiluminescence enzyme immunoassay, and 27 cytokines or chemokines were assayed by the multiplexed BioPlex system. Results Serum IFN-[lambda]^sub 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]^sub 3^ was positively correlated with aspartate aminotransferase, alanine aminotransferase, [alpha]-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 1[alpha] were involved in the sustained viral clearance in PEG-IFN-[alpha] plus RBV therapy; however, serum IFN-[lambda]^sub 3^ levels were not involved. Conclusion Serum IFN-[lambda]^sub 3^ levels are increased in C-CH patients regardless of the IFNL3 genotype. IFN-[lambda]^sub 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.