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In this retrospective observational study, we assessed the effects of fenofibrate (a PPAR\u03b1 agonist) therapy on bile acid metabolism when given to patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) who have had an incomplete response to Ursodiol monotherapy. When fenofibrate was added to Ursodiol therapy there was a significant reduction and in some cases normalization of serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase abnormalities, as well as pro\u2010inflammatory cytokines. Combination fenofibrate treatment also reduced 7\u03b1\u2010hydroxy\u20104\u2010cholesten\u20103\u2010one (C4), the bile acid precursor, as well as total, primary, and conjugated bile acids. In addition, principal components analysis and heatmap analysis show that bile acid metabolites trended closer to that of healthy control subjects. These favorable effects of fenofibrate on bile acid metabolism may contribute to its beneficial clinical effects in patients with PBC and PSC experiencing a subtherapeutic response to Ursodiol monotherapy.<\/jats:p>","DOI":"10.1002\/cpt.1930","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T21:16:00Z","timestamp":1591046160000},"page":"1213-1223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients With Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol"],"prefix":"10.1111","volume":"108","author":[{"given":"Nisanne S.","family":"Ghonem","sequence":"first","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences College of Pharmacy University of Rhode Island Kingston Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6507-237X","authenticated-orcid":false,"given":"Adam M.","family":"Auclair","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences College of Pharmacy University of Rhode Island Kingston Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-211X","authenticated-orcid":false,"given":"Christopher L.","family":"Hemme","sequence":"additional","affiliation":[{"name":"RI\u2010INBRE Bioinformatics Core University of Rhode Island Kingston Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina M.","family":"Gallucci","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences College of Pharmacy University of Rhode Island Kingston Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randolph","family":"de la Rosa Rodriguez","sequence":"additional","affiliation":[{"name":"Liver Center Yale University School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Boyer","sequence":"additional","affiliation":[{"name":"Liver Center Yale University School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Assis","sequence":"additional","affiliation":[{"name":"Liver Center Yale University School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120027"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.90780"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.46.1.121"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/HMER.S91709"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27744"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400346200"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/347645a0"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26155"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2018.06.009"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2011.10.025"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13092"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-9877(86)90137-4"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.11.016"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714519"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300291-JLR200"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.122"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.005389"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.19.2088"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm990554g"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.04.086"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27955"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhbp.281"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0022-2275(20)32398-1","article-title":"Peroxisome proliferator\u2010activated receptor alpha (PPARalpha) and agonist inhibit cholesterol 7alpha\u2010hydroxylase gene (CYP7A1) transcription","volume":"41","author":"Marrapodi M.","year":"2000","journal-title":"J. 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