Tokar Jeffrey L., Berg Carl L.
Digestive Health Center of Excellence, University of Virginia Health System, Lee Street, Charlottesville, VA 22908, USA.
Curr Treat Options Gastroenterol. 2002 Dec;5(6):425-436. doi: 10.1007/s11938-002-0030-1.
Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.
非酒精性脂肪性肝病，包括非酒精性脂肪性肝炎，通常是一种良性、进展缓慢的疾病。然而，在一部分患者中，临床病程可能进展为晚期肝硬化、终末期肝病或肝细胞癌。不幸的是，这些疾病的发病机制、自然史和潜在治疗方法仍知之甚少。确定哪些患者应接受潜在治疗仍然很困难。应考虑进行肝活检以评估肝脏炎症和纤维化程度，因为体格检查结果、生化参数和影像学研究结果与脂肪性肝炎和纤维化的严重程度相关性较差。虽然有一些证据表明肥胖、糖尿病、年龄较大以及天冬氨酸转氨酶与丙氨酸转氨酶比值高于1可能是更严重纤维化的预测指标，但组织学检查仍然是金标准。大多数单纯性肝脂肪变性患者似乎病情良性，可能不需要积极治疗。相反，伴有广泛炎症和纤维化的脂肪性肝炎患者最有可能从有效治疗中获益。最常推荐的治疗方法是减肥。现有数据表明，快速减肥可能会促进肝脏炎症和纤维化；因此，应推荐逐渐减肥。缺乏评估减肥策略长期组织学影响和临床结局的大型随机对照试验。潜在有前景的药物治疗包括胰岛素增敏口服降糖药，如二甲双胍和噻唑烷二酮类药物；降血脂药，如吉非贝齐或3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂；维生素E和其他抗氧化剂；熊去氧胆酸和甜菜碱。与减肥一样，关于这些药物选择疗效的数据有限。此外，没有广泛接受的指南来帮助临床医生在非酒精性脂肪性肝病患者中最佳使用这些药物。
