The search of the drug for the acute severe HBV hepatitis using animal model

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Institute of Physical and Chemical Research (2016-2017); Hiroshima University (2015)
• Principal Investigator: Hiraga Nobuhiko 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 客員研究員 (50625978)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: B型肝炎ウイルス / マウス

Outline of Final Research Achievements

The treatment for acute infection of hepatitis B virus is to control the host immune response and the exclusion of intracellular cccDNA in HBV-infected hepatocytes. The covalently closed circular DNA (cccDNA) forms a stable minichromosome in the nuclei of HBV infected hepatocytes in spite of acute HBV. We established an animal model of fulminant hepatitis caused by HBV infection using human hepatocyte chimeric TK-NOG mice transplanted human peripheral blood monocytes (PBMCs). We found that 1) interferon and nucleotide/nucleoside analogues, which are the main drugs for chronic HBV, are useful for acute HBV. 2) Antibody to HBsAg (anti-HBs) immunoglobulin (HBIG), which can inhibit HBV entry, became hepatitis B surface antigen negative. 3) CTLA4Ig was shown to be effective in suppressing hepatitis. Our results indicate that existing drugs might be useful for treatment for acute HBV.

Free Research Field

肝炎ウイルス