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      Altered Bile Acid Metabolome in Patients with Non-Alcoholic Steatohepatitis

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          Abstract

          Background & Aims

          The prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is increasing at an alarming rate. The role of bile acids in the development and progression of NAFLD to NASH and cirrhosis is poorly understood. This study aimed to quantify the bile acid metabolome in healthy subjects and patients with non-cirrhotic NASH under fasting conditions and after a standardized meal.

          Methods

          Liquid chromatography tandem mass spectroscopy was used to quantify 30 serum and 16 urinary bile acids from 15 healthy volunteers and 7 patients with biopsy-confirmed NASH. Bile acid concentrations were measured at two fasting and four post-prandial timepoints following a high-fat meal to induce gallbladder contraction and bile acid reabsorption from the intestine.

          Results

          Patients with NASH had significantly higher total serum bile acid concentrations than healthy subjects under fasting conditions (2.2- to 2.4-fold increase in NASH; NASH: 2595–3549 μM and healthy: 1171–1458 μM) and at all post-prandial time points (1.7- to 2.2-fold increase in NASH; NASH: 4444–5898 μM and healthy: 2634–2829 μM). These changes were driven by increased taurine- and glycine-conjugated primary and secondary bile acids. Patients with NASH exhibited greater variability in their fasting and post-prandial bile acid profile.

          Conclusions

          Results indicate that patients with NASH have higher fasting and post-prandial exposure to bile acids, including the more hydrophobic and cytotoxic secondary species. Increased bile acid exposure may be involved in liver injury and the pathogenesis of NAFLD and NASH.

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          Author and article information

          Contributors
          Journal
          7902782
          3413
          Dig Dis Sci
          Dig. Dis. Sci.
          Digestive diseases and sciences
          0163-2116
          1573-2568
          4 April 2016
          03 July 2015
          November 2015
          01 November 2016
          : 60
          : 11
          : 3318-3328
          Affiliations
          [1 ]Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, CB #7569 Kerr Hall Chapel Hill, NC 27599
          [2 ]Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Theravance Biopharma US, Inc., 901 Gateway Blvd, South San Francisco, CA 94080
          [3 ]Metabolomics Shared Resource, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813
          [4 ]Department of Biostatistics, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 3105G McGavran-Greenberg Hall, Chapel Hill, NC, 27599
          [5 ]Division of Gastroenterology and Hepatology, UNC School of Medicine, University of North Carolina at Chapel Hill, 8004 Burnett Womack CB #7584, Chapel Hill, NC 27599
          Author notes
          Address Correspondence to: A. Sidney Barritt IV, MD, MSCR, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, 8004 Burnett Womack, CB #7584, Chapel Hill, NC 27599-7584, Tel: (919) 966-2516, Fax: (919) 966-1700, sid_barritt@ 123456med.unc.edu
          Article
          PMC4864493 PMC4864493 4864493 nihpa773583
          10.1007/s10620-015-3776-8
          4864493
          26138654
          aad762ee-b956-4979-8f5f-5533bd505130
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