Elucidation of Molecular Pathogenesis in Childhood-Onset Liver Failure

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08251
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: University of Tsukuba
• Principal Investigator: Imagawa Kazuo 筑波大学, 医学医療系, 講師 (40708509)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肝不全 / 急性肝炎 / 小児 / ゲノム解析

Outline of Final Research Achievements

There are a wide variety of causative diseases of acute hepatitis and subsequent acute liver failure that occur in childhood. However, the cause is still unknown in about half of the cases, and there is no effective treatment other than liver transplantation in cases of fulminant cases. There are many different types of hepatitis, including cases with abnormalities in molecular mechanisms involved in liver metabolism and excretion, and immunogenic hepatitis pathologies triggered by infections and other diseases. Identification of the cause and understanding of the pathogenesis at the molecular level remain unknown. In this study, we performed genome analysis of patients to search for causative genes. We diagnosed diseases that can cause liver failure in childhood, such as progressive familial intrahepatic cholestasis. In addition, activated CD8-positive T cells proliferated in peripheral blood in some cases, and CD8-positive T cells were increased in liver pathology.

Free Research Field

小児肝臓病学

Academic Significance and Societal Importance of the Research Achievements

肝不全を呈する小児における原因検索でゲノム解析が有用であることが示唆された。本研究の過程で免疫原性と思われる急性肝炎の小児において免疫解析を実施したところ、末梢血で活性化CD8陽性T細胞が増殖し、肝臓病理でCD8陽性T細胞が増加していた。なんらかの過剰な免疫応答が急性肝炎の主病態の一つであることが示唆された。これらのように、約半数以上で不明とされる小児の急性肝炎や肝不全における分子レベルでの原因検索方法について本研究で見出すことが出来た。