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）发生在美国人口的2-3%，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，但这些目标的实现是不稳定的，它们与药物干预相结合的相对效果也没有明确的定义。其他形式的治疗包括胰岛素增敏剂，但没有干预被证实或一致接受。此外，对药物治疗结果的解释与通常推荐的患者自愿采用的生活方式改变相混淆。多不饱和脂肪酸，特别是富含omega-3脂肪酸的配方，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，omega - 3脂肪酸通过降低肝脏脂肪含量来改善人类和动物NASH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，而不受体重减轻或运动条件的影响。在常用的补充剂中，富含omega-3的鱼油脱颖而出，因为它获得了美国心脏协会和美国食品和药物管理局的认可，被认为是一种降低冠心病风险的合格健康声明。我们选择的omega-3品牌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相对于运动耐量和体重变化的nash诱导肝损伤综合评分的变化。其他次要终点包括治疗后肝脏脂肪含量、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使用omega-3的主要终点的影响。这项基于gcrc的试点研究包括50名可评估的受试者，将为多中心试验建立一个可行的平台，以衡量自愿改变生活方式对治疗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.