Research on hepatic pathogenesis after achieving SVR by DAA treatment for hepatitis C

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Wakita Takaji 国立感染症研究所, 所長, 所長 (40280789)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: C型肝炎ウイルス

Outline of Final Research Achievements

HCV persistently infects hepatocytes and causes chronic liver damage. As fibrosis progresses, liver lobules are remodeled, and the hemodynamics of the liver also change. Therefore, liver damage caused by persistent HCV infection involves not only viral infection and host immune response, but also changes due to tissue remodeling of the liver. Therefore, even after achieving SVR, liver injury may continue and lead to hepatocarcinogenesis. In this study, we focused on the organelle structure and gene expression changes of infected cells. We constructed HCV-uninfected cells, infected cells, and post-infection-excluded cells on a culture cell basis, and observed HCV elimination from HCV infection. There were genes that changed reversibly and irreversibly in these cells. We will further analyze these cells, analyze human liver chimeric mice and patient specimens, clarify genes that are reversibly and irreversibly changed in common, and clarify host markers related to liver damage.

Free Research Field

肝炎ウイルス

Academic Significance and Societal Importance of the Research Achievements

HCVは抗ウイルス療法により95%以上のウイルス排除率が達成されている。しかし、DAAによるSVR達成後に一部の症例ではウイルス排除後の肝障害の持続や、肝発癌が問題となっている。本研究ではウイルス感染およびウイルス排除に伴う肝細胞および肝組織変化に着目し、ウイルス感染による肝臓の可逆的および不可逆的変化を解析する。ウイルス排除後も回復しない不可逆的変化とその原因となる宿主因子について解明できれば、SVR達成後の肝障害および肝発がん予防に資する検査法および治療法開発につながることが期待される。