Innate immunity and treatment response in chronic viral hepatitis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293169
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Asahina Yasuhiro 東京医科歯科大学, 医歯(薬)学総合研究科, 寄附講座教授 (00422692)
• Co-Investigator(Kenkyū-buntansha): NAKAGAWA Mina 東京医科歯科大学, 医歯学融合教育支援センター, 准教授 (30401342) ; KAKINUMA Sei 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (30372444)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: HCV / IFNλ4 / IL28B

Outline of Final Research Achievements

Interferon (IFN) λ plays an important role in innate immunity to protect against hepatitis C viral (HCV) infection. However, the impact of IFNλs on chronic hepatitis C (CHC) is unknown. We aimed to investigate the mechanism underlying responsiveness to IFN-based therapy in CHC associated with SNPs near IL28B. Intrahepatic expressions of ISGs were significantly up-regulated in nonvirological responders (NRs). IFNλ4 expression was associated with lower IL28B induction in patients with IL28B-unfavorable genotype (p = 0.04) and non-response to IFNα therapy (p = 0.003). Overexpression of IFNλ4 suppressed IL28B induction and promoter activation. These results suggest that impaired induction of IL28B, related to IFNλ4 expression, is associated with non-response to IFNα-based therapy.

Free Research Field

消化器内科学