Phase II study of cholic acid for hepatic steatosis in *

描述（由申请人提供）： 脂肪营养不良是以脂肪组织的选择性损失为特征的病症。 排除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估计患病率低于1000例患者。 肝脂肪变性及其后遗症如肝硬化是这些患者常见的问题。 尽管对糖尿病和高脂血症进行了积极的管理，但肝脏脂肪变性及其并发症在许多患者中仍是一个治疗挑战。 非酒精性脂肪变性尚无既定治疗方法。 最近，重组瘦素治疗报告，以减少肝脏大小和脂肪肝的低瘦素血症患者的脂肪营养不良。 然而，由于并非所有患者都是低肽血症，因此需要开发其他疗法。 胆酸是法尼醇X受体（FXR，NR 1H 4）的有效配体，已显示可减少KK-Ay小鼠（饮食诱导的高胆固醇血症模型）的肝脂肪变性。 以0.5%的剂量给予胆酸3周。 胆酸还降低了该小鼠模型中的血清甘油三酯浓度，并且先前已显示可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然未知。

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.