2019 Fiscal Year Final Research Report
Elucidation of the mechanism involved HBV persistent infection and HBV-related HCC development
| Project/Area Number |
17K09406
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Nitta Sayuri 東京医科歯科大学, 医学部附属病院, 特任助教 (20527056)
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| Co-Investigator(Kenkyū-buntansha) |
柿沼 晴 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (30372444)
朝比奈 靖浩 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)
渡辺 守 東京医科歯科大学, 高等研究院, 特別栄誉教授 (10175127)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | B型肝炎 / 自然免疫応答 |
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| Outline of Final Research Achievements |
HBV (hepatitis B virus) infection causes chronic hepatitis, cirrhosis, and HCC (hepatocellular carcinoma). However, the mechanism involved persistent infection and HCC development are still unclear. In this study, we indicated that innate immunity activated by HBV infection suppressed HBV replication and that the activated innate immune signaling could be partly suppressed by HBV itself, suggesting that the immune evade mechanism by HBV contribute to the persistent infection and resistance to IFN therapy. It may also be associated with the difference of clinical course among the genotypes. In the study using HCC tissue samples and paired non-HCC liver samples, STING mediated signal pathway was suggested to be associated with the HCC development. These results are important for understanding the mechanism of HBV persistent infection and HCC carcinogenesis and also provide the knowledges for developing novel therapeutic agents.
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| Free Research Field |
肝疾患
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| Academic Significance and Societal Importance of the Research Achievements |
本邦におけるHBV（B型肝炎ウイルス）感染者数は未だ140万人程度と非常に多い。HBVの持続感染は慢性肝炎、肝硬変、肝癌の原因となり得るが、ウイルスの完全排除は現在においても困難であることから、これらの機序解明、治療開発が急務である。本研究では、HBVの持続感染成立機序の一端を明らかにしたことで、新たな抗ウイルス薬開発の基盤となる知見を提供でき、またgenotypeによる臨床病態の差異を規定する分子機構に関連する本研究の成果はgenotypeに応じた治療戦略を開発する上で有用と考えられ、社会的意義があると考える。また、肝発癌に新たなメカニズムの関与が示唆され、学術的にも興味深いものである。
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