Pathological deterioration of liver component cells by hepatitis B virus infection and the mechanism of hepatocarcinogenesis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: Kawaguchi Kazunori 金沢大学, 医学系, 特任教授 (90579632)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: B型肝炎ウイルス / 肝細胞癌 / 核酸アナログ / Notchシグナル / HBV cccDNA

Outline of Final Research Achievements

Liver tissue consists from endothelial cells, bile duct cells, immune cells and hepatocyte. Hepatitis B virus induces hepatitis and liver cancer, but the interaction and virus infection related signaling between these component cells are not still clarified. We analyzed these interactions by measuring gene expression in each component cells using single cell gene analysis. We clarified the intercellular signaling including Notch signaling activation and this interaction resulted in the involvement of transcription factors in hepatitis B virus infected cells. Results of analyzing clinical liver tissue found that these transcription factors or intercellular signaling were affected under nucleos(t)ide analogues treatment. In conclusion, intercellular signaling were found to be important in hepatitis B virus infected liver tissue.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

核酸アナログ製剤によりB型肝炎の鎮静化がなされるが、治療後も肝細胞核内に完全二本鎖の形でウイルスが残存しており、発癌や再活性化を引き起こす。この問題を解決するために、肝組織内の構成細胞における感染による変化、細胞間の相互作用やシグナル伝達系を明確にした。本研究はこのウイルス残存の問題を解決し、従来の薬剤では解決できない創薬にも関連するので、社会的意義のある研究となった。