Analysis of IL-6-mediated drug-resistance of hepatitis C virus infection

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590958
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: 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)
• Co-Investigator(Kenkyū-buntansha): ASAHINA Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (00422692) ; WATANABE Mamoru 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
• Co-Investigator(Renkei-kenkyūsha): SAKAMOTO Naoya 北海道大学, 医学研究科, 教授 (10334418)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 治療抵抗性機序 / C型慢性肝炎 / インターロイキン6

Outline of Final Research Achievements

Our previous study described the association of serum IL-6 levels and ER stress and drug-resistance using JFH1 genotype 2a cell culture system. Based on the pTPF1-M170T (LC011929), we constructed full-length 1b clones that expressed core mutant viruses which were clinically resistant to IFN. Although TPF1-M170T clones are not currently allowed in drug-screening tests, perhaps this unique character can assist in establishing the molecular mechanism of HCV replication. We conducted a cohort study to investigate whether serum IL-6 levels influenced treatment outcomes of TVR/PEG-IFN/RBV triple therapy. Our results suggest that baseline low levels of IL-6, as well as their transient increase and decline during early stage of treatment, are correlated to good response to treatment, whereas sustained high levels of serum IL-6 are correlated to treatment resistance in most cases. Taken together, serum IL-6 levels correlate with resistance to treatment also with DAA combination therapy.

Free Research Field

肝臓病学