Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, 32610-0226, USA.
Drugs. 2013 Jan;73(1):1-14. doi: 10.1007/s40265-012-0004-0.
Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disorder in the Western world. It is commonly associated with insulin resistance, obesity, dyslipidaemia, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Nonalcoholic steatohepatitis (NASH) is characterized by steatosis with necroinflammation and eventual fibrosis, which can lead to end-stage liver disease and hepatocellular carcinoma. Its pathogenesis is complex, and involves a state of 'lipotoxicity' in which insulin resistance, with increased free fatty acid release from adipose tissue to the liver, play a key role in the onset of a 'lipotoxic liver disease' and its progression to NASH. The diagnosis of NASH is challenging, as most affected patients are symptom free and the role of routine screening is not clearly established. A complete medical history is important to rule out other causes of fatty liver disease (alcohol abuse, medications, other). Plasma aminotransferase levels and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for a definitive diagnosis. However, there is an active search for plasma biomarkers and imaging techniques that may non-invasively aid in the diagnosis. The treatment of NASH requires a multifaceted approach. The goal is to reverse obesity-associated lipotoxicity and insulin resistance via lifestyle intervention. Although there is no pharmacological agent approved for the treatment of NAFLD, vitamin E (in patients without T2DM) and the thiazolidinedione pioglitazone (in patients with and without T2DM) have shown the most consistent results in randomized controlled trials. This review concentrates on our current understanding of the disease, with a focus on the existing therapeutic approaches and potential future pharmacological developments for NAFLD and NASH.
非酒精性脂肪性肝病（NAFLD）被认为是西方世界最常见的肝脏疾病。它通常与胰岛素抵抗、肥胖、血脂异常、2 型糖尿病（T2DM）和心血管疾病有关。非酒精性脂肪性肝炎（NASH）的特征是脂肪变性伴坏死性炎症和最终纤维化，可导致终末期肝病和肝细胞癌。其发病机制复杂，涉及“脂毒性”状态，其中胰岛素抵抗伴随着脂肪组织向肝脏释放游离脂肪酸，在“脂毒性肝病”的发生及其进展为 NASH 中发挥关键作用。NASH 的诊断具有挑战性，因为大多数受影响的患者无症状，常规筛查的作用也未明确确立。全面的病史对于排除其他原因引起的脂肪肝（酒精滥用、药物、其他）很重要。血浆氨基转移酶水平和肝脏超声有助于 NAFLD/NASH 的诊断，但通常需要肝活检以明确诊断。然而，人们正在积极寻找可能有助于非侵入性诊断的血浆生物标志物和成像技术。NASH 的治疗需要多方面的方法。目标是通过生活方式干预逆转与肥胖相关的脂毒性和胰岛素抵抗。虽然没有批准用于治疗 NAFLD 的药物，但维生素 E（在没有 T2DM 的患者中）和噻唑烷二酮吡格列酮（在有和没有 T2DM 的患者中）在随机对照试验中显示出最一致的结果。这篇综述集中讨论了我们目前对该疾病的理解，重点介绍了现有的治疗方法和 NAFLD 和 NASH 的潜在未来药物治疗进展。
