Te Sligte K., Bourass I., Sels J.P., Driessen A., Stockbrugger R.W., Koek G.H.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
Eur J Intern Med. 2004 Feb;15(1):10-21. doi: 10.1016/j.ejim.2003.12.008.
Non-alcoholic steatohepatitis (NASH) is a metabolic liver disorder that is seen in 2-6% of the general population. It manifests itself by elevated liver enzymes, frequently without symptoms. The histological findings include steatosis, inflammation, fibrosis, and cirrhosis. Three case reports are presented to illustrate features of NASH. A two-hit model has been proposed in the pathogenesis of NASH. The first hit is hepatic steatosis. A hypercaloric diet with high levels of carbohydrates and saturated fatty acids results in elevated plasma free fatty acids (FFA) and expands the adipose tissue. Insulin resistance develops and augments steatosis. Oxidation of FFA yields toxic free radicals, resulting in lipid peroxidation. They cause the second hits: increased oxidative stress on hepatocytes and induction of pro-inflammatory cytokines. When the antioxidant capacities of the liver are insufficient, mitochondrial dysfunction and tumor necrosis factor alpha (TNF-alpha) cause inflammation and fibrosis. Treatment consists of life style modifications, particularly weight loss and exercise. Many drugs have been tried in the treatment of NASH. The insulin-sensitizing drugs metformin, rosiglitazone, and pioglitazone, and the antioxidant vitamin E show promising results. Further investigation of therapeutic options is needed to direct the choice of therapy in the future.
非酒精性脂肪性肝炎（NASH）是一种代谢性肝脏疾病，在普通人群中的发病率为2%至6%。其表现为肝酶升高，通常无明显症状。组织学检查结果包括脂肪变性、炎症、纤维化和肝硬化。本文介绍三例病例报告以说明NASH的特征。NASH发病机制中提出了一种“两次打击”模型。第一次打击是肝脂肪变性。高碳水化合物和饱和脂肪酸的高热量饮食会导致血浆游离脂肪酸（FFA）升高，并使脂肪组织增加。继而出现胰岛素抵抗并加剧脂肪变性。FFA氧化产生有毒自由基，导致脂质过氧化。它们引发第二次打击：肝细胞氧化应激增加和促炎细胞因子的诱导。当肝脏的抗氧化能力不足时，线粒体功能障碍和肿瘤坏死因子α（TNF-α）会导致炎症和纤维化。治疗方法包括改变生活方式，尤其是减肥和锻炼。许多药物已被尝试用于治疗NASH。胰岛素增敏药物二甲双胍、罗格列酮和吡格列酮，以及抗氧化剂维生素E显示出有前景的结果。未来需要进一步研究治疗方案以指导治疗选择。
