Author:
Ahmad Zahid,Subramanyam Lalitha,Szczepaniak Lidia,Simha Vinaya,Adams-Huet Beverley,Garg Abhimanyu
Abstract
ObjectiveHepatic 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.DesignA randomized, double-blind, placebo-controlled, crossover study.MethodsEighteen 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 with1H 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.ResultsCompared 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.ConclusionCA was well tolerated but did not reduce hepatic TG content in patients with lipodystrophy.
Subject
Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism
Cited by
15 articles.
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