Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Gastroenterology, Sanno Hospital, Minato-Ku, Tokyo, Japan.
Expert Opin Emerg Drugs. 2024 Jun;29(2):127-137. doi: 10.1080/14728214.2024.2328036. Epub 2024 Mar 25.
Approved drug therapies for nonalcoholic steatohepatitis (NASH) are lacking, for which various agents are currently being tested in clinical trials. Effective drugs for liver fibrosis, the factor most associated with prognosis in NASH, are important.
This study reviewed the treatment of NASH with a focus on the effects of existing drugs and new drugs on liver fibrosis.
Considering the complex pathophysiology of fibrosis in NASH, drug therapy may target multiple pathways. The method of assessing fibrosis is important when considering treatment for liver fibrosis in NASH. The Food and Drug Administration considers an important fibrosis endpoint to be histological improvement in at least one fibrosis stage while preventing worsening of fatty hepatitis. To obtain approval as a drug for NASH, efficacy needs to be demonstrated on endpoints such as liver-related events and myocardial infarction. Among the current therapeutic agents for NASH, thiazolidinedione, sodium-glucose co-transporter 2, and selective peroxisome proliferator-activated receptors α modulator have been reported to be effective against fibrosis, although further evidence is required. The effects of pan-peroxisome proliferator-activated receptors, obeticholic acid, and fibroblast growth factor-21 analogs on liver fibrosis in the development stage therapeutics for NASH are of particular interest.
目前缺乏非酒精性脂肪性肝炎(NASH)的批准药物疗法,因此目前正在临床试验中测试各种药物。对于与 NASH 预后最相关的肝纤维化,有效的药物非常重要。
本研究重点综述了 NASH 的治疗方法,特别关注现有药物和新药对肝纤维化的影响。
鉴于 NASH 纤维化的复杂病理生理学,药物治疗可能针对多个途径。在考虑 NASH 肝纤维化治疗时,评估纤维化的方法很重要。美国食品和药物管理局(FDA)认为,重要的纤维化终点是组织学上至少改善一个纤维化阶段,同时防止脂肪性肝炎恶化。为了获得 NASH 药物的批准,需要在肝相关事件和心肌梗死等终点上证明疗效。在目前用于 NASH 的治疗药物中,噻唑烷二酮、钠-葡萄糖共转运蛋白 2 和选择性过氧化物酶体增殖物激活受体 α 调节剂已被报道对纤维化有效,但需要更多的证据。全过氧化物酶体增殖物激活受体、奥贝胆酸和成纤维细胞生长因子-21 类似物对 NASH 治疗开发阶段的肝纤维化的影响尤其值得关注。