Identification of Factors Associated with Post-SVR Hepatocellular Carcinoma and Non-Improvement of Liver Fibrosis in Hepatitis C, and Therapeutic Implications

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17008
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hokkaido University
• Principal Investigator: Kawagishi Naoki 北海道大学, 医学研究院, 客員研究員 (90849374)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: HCV / 肝癌 / 肝線維化

Outline of Final Research Achievements

We identified multiple miRNA expression changes strongly associated with post-SVR HCC and involved in the improvement of liver fibrosis after SVR. We demonstrated that these miRNAs have anti-fibrotic effects through the deactivation of hepatic stellate cells. Furthermore, we investigated the potential of administering these miRNAs to a liver fibrosis model mouse, revealing their ability to suppress liver fibrosis. Additionally, we identified the association between non-improvement of liver fibrosis and increased expression of ANG2 mediated through portal hypertension. In a long-term observational study, we also reported the correlation between increased ANG2 expression and non-improvement of liver fibrosis. Considering the potential association between non-improvement of liver fibrosis and hepatocellular carcinoma, we examined the relationship between post-SVR hepatocellular carcinoma and increased ANG2 expression.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

慢性C型肝炎に対する、Direct Acting Antiviral(DAA)の登場により治療の安全性・効果は飛躍的に上昇し非代償性肝硬変症例を含め大多数の症例においてウイルス学的著効(SVR)が得られるようになった。SVR症例は、多くが肝線維化の改善と肝発癌率の低下が期待されるが一部の症例においてはSVR後も肝線維化悪化・肝発癌が認めらえる。しかしながら、現在までにSVR後の肝線維化悪化、肝発癌を予測する因子については十分に明らかとされていない。今研究で得られた結果により、SVR後発癌予防、肝線維化改善のターゲットの同定と治療応用への萌芽的知見が得られた。