Kim Won
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Division of Gastroenterology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
Korean J Gastroenterol. 2017 Jun 25;69(6):353-358. doi: 10.4166/kjg.2017.69.6.353.
The prevalence of non-alcoholic fatty liver disease (NAFLD) has sharply increased over the past several decades in Korea. In most cases of NAFLD, metabolic stress and cellular apoptosis are often driven by metabolic abnormality, eventually leading to inflammation and fibrosis . Along with a dramatic surge in the obesity epidemic, 10-20% of NAFLD patients ultimately progress to non-alcoholic steatohepatitis (NASH), a precursor to cirrhosis and hepatocellular carcinoma, as well as multi-organ systemic diseases. Currently, diet and exercise are chiefly recommended to achieve significant weight loss and improve metabolic dysfunction in patients with NAFLD. However, weight loss remains to be an elusive goal for both clinical practitioners and NAFLD patients. To date, although there has not been any proven pharmacotherapy against NAFLD, numerous promising pipelines with good target engagement are under development. Moreover, given the global landmark phase 3 trials using obeticholic acid (a farnesoid X receptor agonist, REGENERATE trial) and elafibranor (a dual peroxisome proliferator-activated receptor α/δ agonist, RESOLVE-IT trial), the era of specific target therapies focusing on molecular and metabolic pathogenesis of NASH and fibrosis is near at hand. In this paper, we briefly cover the current and future therapeutic options in patients with NAFLD across the entire spectrum of diseases.
在过去几十年里,韩国非酒精性脂肪性肝病(NAFLD)的患病率急剧上升。在大多数NAFLD病例中,代谢应激和细胞凋亡通常由代谢异常驱动,最终导致炎症和纤维化。随着肥胖流行率的急剧上升,10%-20%的NAFLD患者最终会进展为非酒精性脂肪性肝炎(NASH),这是肝硬化和肝细胞癌以及多器官系统性疾病的先兆。目前,主要建议通过饮食和运动来实现显著的体重减轻,并改善NAFLD患者的代谢功能障碍。然而,体重减轻对临床医生和NAFLD患者来说仍然是一个难以实现的目标。迄今为止,虽然尚未有任何经证实的针对NAFLD的药物治疗方法,但许多具有良好靶点结合效果的有前景的研发管线正在进行中。此外,鉴于使用奥贝胆酸(一种法尼醇X受体激动剂,REGENERATE试验)和依拉非尼(一种过氧化物酶体增殖物激活受体α/δ双重激动剂,RESOLVE-IT试验)的全球标志性3期试验,专注于NASH和纤维化分子及代谢发病机制的特异性靶向治疗时代即将来临。在本文中,我们简要介绍了NAFLD患者在整个疾病谱中的当前和未来治疗选择。