Phase II study of cholic acid for hepatic steatosis in *

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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.