Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, VA, USA.
Therap Adv Gastroenterol. 2010 Mar;3(2):121-37. doi: 10.1177/1756283X09359964.
Nonalcoholic fatty liver disease (NAFLD) has become increasingly recognized as the most common cause of abnormal liver enzymes in the last few decades and is among the most common forms of chronic liver disease in the Western world and across the globe. With the growing epidemic of obesity and diabetes, NAFLD is estimated to affect about one-quarter of the US population. Although most patients with NAFLD have nonprogressive bland steatosis, a minority of patients develop the histological subtype of nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis, hepatocellular carcinoma, and liver-related death. This is especially true when NASH patients have type 2 diabetes. Treatment of NAFLD should therefore be directed towards patients with established NASH. Sustained weight loss seems to improve insulin resistance and associated NASH. In fact, weight loss with bariatric surgery leads to biochemical and histological improvement in morbidly obese patients with NASH. Several pharmacologic agents have been studied in an effort to improve insulin resistance and pro-inflammatory mediators potentially responsible for the development and progression of NASH. While some studies have shown initial promise, none has established long-term efficacy using randomized clinical trials. This paper briefly reviews the epidemiology, natural history, and pathophysiology of NAFLD and NASH and then focuses on the clinical trials of various therapeutic modalities for NAFLD. These include weight loss agents, bariatric surgery, insulin-sensitizing agents, lipid-lowering agents, antioxidants, probiotics, anti-tumor necrosis factor agents, cytoprotective and other novel agents.
非酒精性脂肪性肝病（NAFLD）在过去几十年中已被越来越多地认为是导致肝酶异常的最常见原因，并且是非酒精性脂肪性肝炎（NASH）在西方世界和全球范围内最常见的慢性肝病形式之一。随着肥胖症和糖尿病的流行，估计有四分之一的美国人口患有 NAFLD。尽管大多数 NAFLD 患者的非进展性肝脂肪变性，但少数患者会出现非酒精性脂肪性肝炎（NASH）的组织学亚型，这可能进展为肝硬化、肝细胞癌和与肝脏相关的死亡。当 NASH 患者患有 2 型糖尿病时尤其如此。NAFLD 的治疗因此应针对已确诊的 NASH 患者。持续的体重减轻似乎可以改善胰岛素抵抗和相关的 NASH。事实上，肥胖症患者通过减肥手术减轻体重可以改善 NASH 的生化和组织学。已经研究了几种药物来改善胰岛素抵抗和可能导致 NASH 发展和进展的促炎介质。虽然一些研究显示出初步的希望，但没有一项研究通过随机临床试验证明长期疗效。本文简要回顾了 NAFLD 和 NASH 的流行病学、自然史和病理生理学，然后重点介绍了各种治疗方法治疗 NAFLD 的临床试验。这些方法包括减肥药物、减肥手术、胰岛素增敏剂、降脂药物、抗氧化剂、益生菌、抗肿瘤坏死因子药物、细胞保护剂和其他新型药物。
