Nakajima Kei
Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Saitama, Sakado 350-0295, Japan.
Int J Hepatol. 2012;2012:950693. doi: 10.1155/2012/950693. Epub 2012 Dec 9.
Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.
非酒精性脂肪性肝病(NAFLD)和非酒精性脂肪性肝炎(NASH)是多学科肝脏疾病,常伴有2型糖尿病或代谢综合征,其特征为胰岛素抵抗。因此,2型糖尿病和代谢综合征的有效治疗不仅应针对心脏代谢异常,还应针对相关的肝脏疾病。在过去十年中,已表明二甲双胍、噻唑烷二酮类、维生素E、依泽替米贝、n-3多不饱和脂肪酸、肾素-血管紧张素系统(RAS)阻滞剂和抗肥胖药物可改善肝脏病理生理紊乱以及临床参数。因此,胰岛素增敏剂、抗氧化剂、尼曼-匹克C1样1(NPC1L1)抑制剂、RAS阻滞剂以及靶向中枢神经系统的药物可能是NAFLD以及可能的NASH的候选药物治疗方法。然而,这些药物长期治疗(可能长达数年)的疗效、安全性和耐受性尚未完全确立。此外,临床试验尚未全面研究降脂药物(即他汀类、贝特类和NPC1L1抑制剂)治疗NAFLD的疗效。尽管RAS阻滞剂和基于肠促胰岛素的药物(胰高血糖素样肽-1类似物和二肽基肽酶-4抑制剂)的临床证据也不足,但这些药物在具有胰岛素增敏和抗炎作用且不导致体重增加方面很有前景。