Omega-3 Fish Oil for Nonalcoholic Steatohepatitis

描述（由申请人提供）：非酒精性脂肪性肝炎（NASH）发生在2-3%的美国人口中，并有15-20%的机会进展为肝硬化。它与肥胖、高脂血症和胰岛素抵抗密切相关。治疗通常包括建议增加运动和开始减肥饮食，但这些目标是暂时实现的，其与药物干预的相对效果尚未明确。其他形式的治疗包括胰岛素增敏剂，但没有干预措施被证明或统一接受。此外，药物治疗结果的解释受到患者自愿采取的通常建议的生活方式改变的混淆。多不饱和脂肪酸，特别是富含ω-3脂肪酸的制剂，因其对高脂血症和降低冠心病风险的有益作用而被医学界广泛接受和认可。最近的数据表明，ω 3脂肪酸通过降低肝脏脂肪含量来改善人类和NASH动物模型中的肝脏脂肪变性。我们假设，与安慰剂相比，omega-3脂肪酸（3g/天）将改善NASH活性，肝脏脂肪含量和脂质谱，而不依赖于体重减轻或运动调节。在常用的补充剂中，富含omega-3的鱼油脱颖而出，赢得了美国心脏协会的认可，并获得FDA批准，成为降低冠状动脉风险的合格健康声明。我们选择了一个品牌的omega-3，超过了欧洲和斯堪的纳维亚医学标准规定的纯度标志，并符合NCCAM最近采用的标准。我们的主要终点是评估NASH诱导的肝损伤的复合评分相对于运动耐量和体重变化的变化。其他次要终点包括治疗后通过MRI测量的肝脏脂肪含量、血脂谱、胰岛素敏感性和代谢综合征标志物的变化。将进行统计分析，以评估体重减轻和运动耐量变化对主要终点（相对于omega-3使用）的影响。这项基于GCRC的50例可评价受试者的初步研究将为多中心试验建立一个可行的平台，以测量自愿生活方式改变对治疗NASH的潜在有效药物治疗的相对影响。

DESCRIPTION (provided by applicant): Nonalcoholic steatohepatitis (NASH) occurs in 2-3% of the US population and carries a 15-20% chance of progression to cirrhosis. It is closely associated with obesity, hyperlipidemia and insulin resistance. Therapy usually includes recommendations to increase exercise and to begin weight reducing diets but these goals are variably achieved and their relative effects in conjunction with pharmacological intervention have not been well-defined. Other forms of therapy include insulin sensitizing agents but no intervention is proven or uniformly accepted. Furthermore, interpretation of pharmacological treatment results is confounded by commonly recommended life-style changes voluntarily adopted by the patient. Polyunsaturated fatty acids, especially formulations rich in omega-3 fatty, are widely accepted and endorsed in the medical community for their beneficial effects on hyperlipidemia and coronary disease risk reduction. Recent data suggests that omega 3 fatty acids ameliorate hepatic steatosis in humans and in animal models of NASH by reducing hepatic fat content. We hypothesize that omega-3 fatty acid (3g/day) will produce improvement in NASH activity, liver fat content, and lipid profiles independent of weight loss or exercise conditioning compared to a placebo. Among commonly used supplements, omega-3 rich fish oils stand out as having won endorsement from the American Heart Association and FDA approval for a qualified health claim in coronary risk reduction. We have chosen a brand of omega-3 that exceeds purity marks set by European and Scandanavian Medicinal Standards and meets recently adopted criteria set by NCCAM. Our primary endpoint is to assess changes in a composite score of NASH-induced liver injury relative to changes in exercise tolerance and weight. Other secondary endpoints include changes in liver fat content by MRI, blood lipid profile, insulin sensitivity and markers of the metabolic syndrome after treatment. Statistical analysis will be performed to assess the impact of weight loss and changes in exercise tolerance on the primary endpoint relative to omega-3 use. This GCRC-based pilot study of 50 evaluable subjects will establish a workable platform for multicenter trials to measure the relative impact of voluntary life-style modification on potentially effective pharmacological therapy in treating NASH.