Le Thuy-Anh, Loomba Rohit
Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
J Clin Exp Hepatol. 2012 Jun;2(2):156-73. doi: 10.1016/S0973-6883(12)60104-2. Epub 2012 Jul 21.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes and chronic liver disease in the US with expected rise in incidence paralleling the epidemic of obesity. A subset of patients with NAFLD have the progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH), which is characterized by specific features on liver histology including hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis can progress to cirrhosis and result in liver-related death. Insulin resistance is commonly seen in patients with NASH and often co-exists with other features of the metabolic syndrome including hypertension, hyperlipidemia, and obesity. Although weight loss through lifestyle modifications including dietary changes and increased physical exercise remains the backbone of management of NASH, it has proved challenging for patients to achieve and maintain weight loss goals. Thus, it is often necessary to couple lifestyle changes with another pharmacologic treatment for NASH. Insulin sensitizers including the biguanides (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon-like peptide-1 receptor agonists (exenatide) are large groups of medications that have been studied for the treatment of NASH. Other agents with anti-inflammatory, anti-apoptotic, or anti-fibrotic properties which have been studied in NASH include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review will provide a detailed summary on the clinical data behind the full spectrum of treatments that exist for NASH and suggest management recommendations.
非酒精性脂肪性肝病(NAFLD)是美国肝酶异常和慢性肝病的最常见原因,预计其发病率的上升将与肥胖流行趋势同步。一部分NAFLD患者患有进展性NAFLD,即非酒精性脂肪性肝炎(NASH),其特征是肝脏组织学具有特定特征,包括肝细胞气球样变性、小叶炎症以及3区脂肪变性,伴有或不伴有窦周纤维化。非酒精性脂肪性肝炎可进展为肝硬化并导致肝脏相关死亡。胰岛素抵抗在NASH患者中很常见,且常与代谢综合征的其他特征并存,包括高血压、高脂血症和肥胖。尽管通过包括饮食改变和增加体育锻炼在内的生活方式调整来减轻体重仍然是NASH管理的核心,但事实证明,患者要实现并维持体重减轻目标具有挑战性。因此,通常有必要将生活方式改变与另一种NASH药物治疗相结合。胰岛素增敏剂包括双胍类(二甲双胍)、噻唑烷二酮类(吡格列酮和罗格列酮)以及胰高血糖素样肽-1受体激动剂(艾塞那肽),这些都是已被研究用于治疗NASH的大类药物。在NASH中已被研究的其他具有抗炎、抗凋亡或抗纤维化特性的药物包括维生素E、己酮可可碱、甜菜碱和熊去氧胆酸。本综述将详细总结NASH现有各种治疗方法背后的临床数据,并提出管理建议。