TY - JOUR
T1 - Cholic acid for hepatic steatosis in patients with lipodystrophy
T2 - A randomized, controlled trial
AU - Ahmad, Zahid
AU - Subramanyam, Lalitha
AU - Szczepaniak, Lidia
AU - Simha, Vinaya
AU - Adams-Huet, Beverley
AU - Garg, Abhimanyu
PY - 2013/5
Y1 - 2013/5
N2 - 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. Design: 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 1H 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. Conclusion: CAwas well tolerated but did not reduce hepatic TG content in patients with lipodystrophy.
AB - 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. Design: 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 1H 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. Conclusion: CAwas well tolerated but did not reduce hepatic TG content in patients with lipodystrophy.
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U2 - 10.1530/EJE-12-0969
DO - 10.1530/EJE-12-0969
M3 - Article
C2 - 23447519
AN - SCOPUS:84877123938
SN - 0804-4643
VL - 168
SP - 771
EP - 778
JO - European journal of endocrinology
JF - European journal of endocrinology
IS - 5
ER -