• Open Access

Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial

Authors

  • Thuy-Anh Le,

    1. Division of Gastroenterology, Department of Medicine,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • Joshua Chen,

    1. Department of Radiology,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • Christopher Changchien,

    1. Department of Radiology,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • Michael R. Peterson,

    1. Department of Pathology,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • Yuko Kono,

    1. Division of Gastroenterology, Department of Medicine,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • Heather Patton,

    1. Division of Gastroenterology, Department of Medicine,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • Benjamin L. Cohen,

    1. Division of Gastroenterology, Department of Medicine,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • David Brenner,

    1. Division of Gastroenterology, Department of Medicine,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • Claude Sirlin,

    1. Department of Radiology,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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  • Rohit Loomba,

    Corresponding author
    1. Division of Gastroenterology, Department of Medicine,Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
    2. Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
    • Division of Gastroenterology and Epidemiology, University of California at San Diego School of Medicine, UC 303, MC-063, 9500 Gilman Drive, La Jolla, CA 92093===

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    • fax: 858-534-3338. (fattyliver.ucsd.edu)

  • for the San Diego Integrated NAFLD Research Consortium (SINC)


  • Potential conflict of interest: Nothing to report.

Abstract

Bile acid sequestrants (BAS) lower plasma low density lipoprotein levels and improve glycemic control. Colestimide, a BAS, has been claimed by computed tomography to reduce liver fat. Therefore, we examined the efficacy of colesevelam, a potent BAS, to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liver fat was measured by a novel magnetic resonance imaging (MRI) technique, the proton-density-fat-fraction (PDFF), as well as by conventional MR spectroscopy (MRS). Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 g/day orally or placebo for 24 weeks. The primary outcome was change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Compared with placebo, colesevelam increased liver fat by MRI-PDFF in all nine segments of the liver with a mean difference of 5.6% (P = 0.002). We cross-validated the MRI-PDFF-determined fat content with that assessed by colocalized MRS; the latter showed a mean difference of 4.9% (P = 0.014) in liver fat between the colesevelam and the placebo arms. MRI-PDFF correlated strongly with MRS-determined hepatic fat content (r2 = 0.96, P < 0.0001). Liver biopsy assessment of steatosis, cellular injury, and lobular inflammation did not detect any effect of treatment. Conclusion: Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR-detected increase in liver fat has clinical consequences is not known. (HEPATOLOGY 2012;56:922–932)

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