Liver cancer research in non-alcoholic fatty liver disease

• Project/Area Number: 18K15790
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Yokohama City University
• Principal Investigator: HONDA Yasushi 横浜市立大学, 医学部, 助教 (00784844)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: NAFLD / NASH / HCC / 肝細胞癌 / 化学予防

Outline of Final Research Achievements

We developed a new hepatocarcinogenesis model (DEN+AMLN model) with obesity, insulin resistance, and liver fibrosis using the AMLN model, which is a food-induced model similar to the human NAFLD/NASH. We used the liver chemo-carcinogen diethylnitrosamine and B6C3F1 mice for chemoprevention using SGLT2 inhibitors and PPARα, which are potential therapeutic agents for NAFLD, and also examined differences in carcinogenesis due to differences in diet.

Academic Significance and Societal Importance of the Research Achievements

原発性肝がんの約90%を肝細胞癌が占め、その多くはB型およびC型肝炎ウイルスによるものである。近年、ウイルス性肝炎のない非B非C肝癌が増加しており、NASH由来の肝細胞癌が原因と考えらえている。NAFLD/NASHの病態は未だ不明な部分も多く、NASH由来の肝細胞癌についても同様である。我々はこれまでにNASHのマウスモデルを用いて、NASHの薬物治療について検討を行ってきた。近年、ウイルス性肝炎のない非B非C肝癌が増加しており、この背景にはNAFLDの増加が原因と考えらえており、その対応が急務である。