Identification of NASH patients who obtain therapeutic benefit from the improvement of nocturnal intermittent hypoxia and its application for clinical practice.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: The Nippon Dental University
• Principal Investigator: Hirono Haruka 日本歯科大学, 新潟生命歯学部, 准教授 (80386268)
• Co-Investigator(Kenkyū-buntansha): 大越 章吾 日本歯科大学, 新潟生命歯学部, 教授 (70231199) ; 長谷川 勝彦 日本歯科大学, 新潟生命歯学部, 准教授 (60328870) ; 河野 正己 日本歯科大学, 新潟生命歯学部, 教授 (20170201) ; 石川 博 筑波大学, 医学医療系, 研究員 (30089784)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 閉塞性睡眠時無呼吸症 / 慢性間欠的低酸素 / 非アルコール性脂肪性肝疾患 / 非アルコール性脂肪肝炎 / 持続陽圧呼吸

Outline of Final Research Achievements

Obstructive sleep apnea (OSA) is a condition in which patients are a state of chronic intermittent hypoxia (CIH), and OSA is well known to be highly complicated with non-alcoholic fatty liver disease (NAFLD). We previously reported that the improvement of CIH by continuous positive airway pressure (CPAP) significantly improved the liver injury in the OSA patients with NAFLD, which could suppress the　progression from NAFLD to NASH. In this animal study, the mice with NAFLD were deeply associated with expression of RANTES (regulated on activation normally T-cell expressed and secreted), which is one of the arteriosclerosis factors. And CPAP in good compliance improved RANTES in serum of the OSA patients with NAFLD. Therefore, CIH and NAFLD, and arteriosclerosis might be strongly correlated, and the improvement of CIH by CPAP could clinically suppress the progression of arteriosclerosis in OSA patients with NAFLD.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

NAFLDを合併したOSA患者の血清において、CPAP施行後のRANTESが有意に低下していたことから、CPAPという薬物療法によらない治療法がOSAを有するNAFLDの患者の動脈硬化の進展予防法にもなる可能性があり、有効な治療法がないNAFLDにおいてこの研究の社会的意義は大きい。今回の夜間低酸素の病態解析を切り口にして、今後、CIHとNAFLD、そして動脈硬化の3者の病態ネットワークが明らかになれば、この研究の学術的意義は大きいと思われる。