title: Cholic acid for hepatic steatosis in patients with lipodystrophy: a randomized, controlled trial.
abstract: OBJECTIVE
  Hepatic steatosis is a common complication in patients with lipodystrophies and can lead to cirrhosis. There is no proven effective therapy for hepatic steatosis, but cholic acid (CA), a farnesoid X receptor agonist, has previously been shown to reduce hepatic triglyceride (TG) content in mice and serum TG in humans. Our objective was to assess clinical efficacy and tolerability of CA therapy in patients with lipodystrophy and hepatic steatosis.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, crossover study.
  
  
  METHODS
  Eighteen patients with genetic or autoimmune lipodystrophies and elevated hepatic TG content participated in the study. The intervention was CA (15 mg/kg per day) compared with placebo for a period of 6 months each. Hepatic TG content, the primary outcome variable, was measured with (1)H magnetic resonance spectroscopy at baseline and at 3 and 6 months during each study period. Levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and TG were secondary end points of the study.
  
  
  RESULTS
  Compared with placebo, CA did not reduce (median (interquartile range) hepatic TG content (14.8% (9.4-19.0%) vs 15.9% (10.5-26.5%) respectively; P=0.42) or serum TG ((340 mg/dl (233-433 mg/dl) vs 390 mg/dl (233-595 mg/dl) respectively; P=0.45)). CA therapy also did not change AST, ALT, or GGT levels. Two patients developed diarrhea and excessive flatus while taking CA and these symptoms resolved after reducing the dose of CA.
  
  
  CONCLUSIONS
  CA was well tolerated but did not reduce hepatic TG content in patients with lipodystrophy.
authors: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Zahid
authors: Z
authors: Ahmad
authors: Lalitha
authors: L
authors: Subramanyam
authors: Lidia
authors: L
authors: Szczepaniak
authors: Vinaya
authors: V
authors: Simha
authors: Beverley
authors: B
authors: Adams-Huet
authors: Abhimanyu
authors: A
authors: Garg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D019826:Cholic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D008060:Lipodystrophy / Q000150:complications* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D014280:Triglycerides; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019826:Cholic Acid