{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:06Z","timestamp":1786977966796,"version":"build-2736575974"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>\n                    Accumulation of cytotoxic bile acids (BAs) during cholestasis can result in liver failure. Glucuronidation, a phase II metabolism pathway responsible for BA detoxification, is regulated by peroxisome proliferator\u2013activated receptor alpha (PPAR\u03b1). This study investigates the efficacy of adjunct fenofibrate therapy to up\u2010regulate BA\u2010glucuronidation and reduce serum BA toxicity during cholestasis. Adult patients with primary biliary cholangitis (PBC, n\u00a0=\u00a032) and primary sclerosing cholangitis (PSC, n\u00a0=\u00a023), who experienced an incomplete response while receiving ursodiol monotherapy (13\u201015\u00a0mg\/kg\/day), defined as serum alkaline phosphatase (ALP)\u00a0\u2265\u00a01.5 times the upper limit of normal, received additional fenofibrate (145\u2010160\u00a0mg\/day) as standard of care. Serum BA and BA\u2010glucuronide concentrations were measured by liquid chromatography\u2013mass spectrometry. Combination therapy with fenofibrate significantly decreased elevated serum ALP (\u221276%,\n                    <jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>\n                    &lt;\u00a00.001), aspartate transaminase, alanine aminotransferase, bilirubin, total serum BAs (\u221254%), and increased serum BA\u2010glucuronides (+2.1\u2010fold,\n                    <jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>\n                    &lt;\u00a00.01) versus ursodiol monotherapy. The major serum BA\u2010glucuronides that were favorably altered following adjunct fenofibrate include hyodeoxycholic acid\u20136G (+3.7\u2010fold,\n                    <jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>\n                    &lt;\u00a00.01), hyocholic acid\u20136G (+2.6\u2010fold,\n                    <jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>\n                    &lt;\u00a00.05), chenodeoxycholic acid (CDCA)\u20133G (\u221236%), and lithocholic acid (LCA)\u20133G (\u221242%) versus ursodiol monotherapy. Fenofibrate also up\u2010regulated the expression of uridine 5\u2032\u2010diphospho\u2010glucuronosyltransferases and multidrug resistance\u2013associated protein 3 messenger RNA in primary human hepatocytes. Pearson\u2019s correlation coefficients identified strong associations between serum ALP and metabolic ratios of CDCA\u20103G (r\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0=\u00a00.62,\n                    <jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>\n                    &lt;\u00a00.0001), deoxycholic acid (DCA)\u20103G (r\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0=\u00a00.48,\n                    <jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>\n                    &lt;\u00a00.0001), and LCA\u20103G (r\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0=\u00a00.40,\n                    <jats:italic toggle=\"yes\">P\u00a0<\/jats:italic>\n                    &lt;\u00a00.001), in ursodiol monotherapy versus control. Receiver operating characteristic analysis identified serum BA\u2010glucuronides as measures of response to therapy.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Fenofibrate favorably alters major serum BA\u2010glucuronides, which correlate with reduced serum ALP levels and improved outcomes. A PPAR\u03b1\u2010mediated anti\u2010cholestatic mechanism is involved in detoxifying serum BAs in patients with PBC and PSC who have an incomplete response on ursodiol monotherapy and receive adjunct fenofibrate. Serum BA\u2010glucuronides may serve as a noninvasive measure of treatment response in PBC and PSC.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1787","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T05:16:17Z","timestamp":1630041377000},"page":"2035-2051","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":25,"title":["Adjunct Fenofibrate Up\u2010regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis"],"prefix":"10.1097","volume":"5","author":[{"given":"Gina M.","family":"Gallucci","sequence":"first","affiliation":[{"name":"College of Pharmacy, Biomedical and Pharmaceutical Sciences,University of Rhode Island,Kingston,RI,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Trottier","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology,Endocrinology and Nephrology Axis,CHU de Qu\u00e9bec Research Center,Laval,Qu\u00e9bec,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Hemme","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Biomedical and Pharmaceutical Sciences,University of Rhode Island,Kingston,RI,USA"},{"name":"RI\u2010INBRE Bioinformatics Core,Kingston,RI,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Assis","sequence":"additional","affiliation":[{"name":"Yale School of Medicine,Liver Center,New Haven,CT,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Yale School of Medicine,Liver Center,New Haven,CT,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Barbier","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology,Endocrinology and Nephrology Axis,CHU de Qu\u00e9bec Research 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