Phase II study of cholic acid for hepatic steatosis in *

描述(由申请人提供)： 脂肪营养不良是一种以选择性脂肪组织丢失为特征的疾病。不包括患有脂肪营养不良的HIV感染患者，美国其他遗传性和获得性脂肪营养不良的患病率估计不到1000名患者。肝脏脂肪变性及其后遗症如肝硬变是这些患者的常见问题。尽管积极治疗糖尿病和高脂血症，但肝脏脂肪变性及其并发症对许多患者的治疗提出了挑战。目前还没有针对非酒精性脂肪变性的既定疗法。最近，重组瘦素疗法被报道能缩小伴有脂营养不良的低蛋白血症患者的肝脏大小和肝脏脂肪变性。然而，由于并不是所有的患者都是低蛋白血症，因此有必要开发其他治疗方法。胆酸是法尼类X受体(FXR，NR1H4)的有效配体，已被证明可以减轻KK-Ay小鼠(一种饮食诱导的高甘油三酯血症模型)的肝脏脂肪变性。胆酸剂量为0.5%，疗程3周。胆酸还可以降低这个小鼠模型中的血清甘油三酯浓度，此前已有研究表明，胆酸可以降低高甘油三酯血症患者的血清甘油三酯。胆酸在减少人类肝脏脂肪变性方面的有效性仍不清楚。

DESCRIPTION (provided by applicant): Lipodystrophies are disorders characterized by selective loss of adipose tissue. Exluding HIV-infected patients with lipodystrophies, the estimated prevalence of other genetic and acquired lipodystrophies in the U.S. is less than 1000 patients. Hepatic steatosis and its sequelae such as cirrhosis are common problems in these patients. Despite aggressive management of diabetes and hyperlipidemia, hepatic steatosis and its complications present a therapeutic challenge in many patients. There is no established therapy for nonalcoholic steatosis. Recently, recombinant leptin therapy was reported to reduce liver size and hepatic steatosis in hypoleptinemic patients with lipodystrophies. However, since all patients are not hypoleptinemic, there is need to develop other therapies. Cholic acid which is a potent ligand for farnesoid X receptor (FXR, NR1H4) has been shown to reduce hepatic steatosis in KK-Ay mice (a model for diet-induced hypertriglyceridemia). Cholic acid was given in a dose of 0.5% for 3 weeks. Cholic acid also reduced serum triglyceride concentration in this mouse model and has been previously shown to reduce serum triglyceride in patients with hypertriglyceridemia. The effectiveness of cholic acid in reducing hepatic steatosis in humans remains unknown.