{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:47:59Z","timestamp":1776185279090,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Total bilirubin is a predictor of survival in primary biliary cholangitis, with the main elevated component being direct bilirubin. The purpose of this post hoc analysis was to assess the efficacy and safety of obeticholic acid across quartiles of varying baseline levels of direct bilirubin in the phase 3, randomized, placebo\u2010controlled Primary Biliary Cholangitis Obeticholic Acid International Study of Efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This analysis assessed patients on the basis of their baseline direct bilirubin level (divided by quartile). Biochemistry and safety outcomes were evaluated within each quartile over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the quartile with the highest baseline direct bilirubin (&gt;5.47\u00a0\u00b5mol\/L), there was a significant reduction in both direct and total bilirubin at Month 12 compared with placebo. Least squares mean (standard error) change from baseline in direct bilirubin at Month 12 was 4.17 (1.42) \u00b5mol\/L for placebo, \u22123.48 (1.63) \u00b5mol\/L for obeticholic acid 5\u201010\u00a0mg and \u22123.66 (1.51) \u00b5mol\/L for obeticholic acid 10\u00a0mg (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001, obeticholic acid vs placebo); the corresponding values for total bilirubin at Month 12 were 4.38 (1.55) \u00b5mol\/L for placebo, \u22124.53 (1.83) \u00b5mol\/L for obeticholic acid 5\u201010\u00a0mg and \u22125.06 (1.64) \u00b5mol\/L for obeticholic acid 10\u00a0mg (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001, obeticholic acid vs placebo).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Obeticholic acid treatment was associated with significant reductions in total and direct bilirubin, particularly in patients with high baseline direct bilirubin. Because raised direct bilirubin levels, even within the normal range, are predictive of survival in primary biliary cholangitis, these results suggest substantial benefits of obeticholic acid in at\u2010risk patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14429","type":"journal-article","created":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T21:40:14Z","timestamp":1583617214000},"page":"1121-1129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Reduction and stabilization of bilirubin with obeticholic acid treatment in patients with primary biliary cholangitis"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5413-9687","authenticated-orcid":false,"given":"Albert","family":"Par\u00e9s","sequence":"first","affiliation":[{"name":"Hospital Clinic University of Barcelona IDIBAPS CIBERehd Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell","family":"Shiffman","sequence":"additional","affiliation":[{"name":"Liver Institute of Virginia Bon Secours Mercy Health Newport News VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Vargas","sequence":"additional","affiliation":[{"name":"Liver Unit Hospital Vall d'Hebron Universitat Aut\u00f2noma de Barcelona CIBERehd Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3262-1998","authenticated-orcid":false,"given":"Pietro","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Center for Autoimmune Liver Diseases San Gerardo Hospital Department of Medicine and Surgery University of Milano\u2010Bicocca Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth S.","family":"Malecha","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Liberman","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leigh","family":"MacConell","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gideon","family":"Hirschfield","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease Toronto General Hospital and Department of Medicine University of Toronto Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020712-164014"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30145"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/HMER.S135337"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22906"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.01.029"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.08.029"},{"key":"e_1_2_11_9_1","first-page":"41A","article-title":"Bilirubin is predictive of transplant\u2010free survival even within the normal range in primary biliary cholangitis patients","volume":"66","author":"Murillo Perez CF","year":"2017","journal-title":"Hepatology"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28017"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22428"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.02.031"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/jlts.2002.35927"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315259"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230532"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.01.003"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.07.061"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22517"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2147\/HMER.S91709"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2012.18.4.375"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i25.7683"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000463"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.517"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000003114"},{"key":"e_1_2_11_25_1","unstructured":"Intercept Pharmaceuticals.OCALIVA [package insert].New York NY:Intercept Pharmaceuticals;2018."},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509840"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm025529g"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29569"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.12.005"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30094-9"},{"key":"e_1_2_11_31_1","unstructured":"Clinicaltrials.gov.Phase 4 study of obeticholic acid evaluating clinical outcomes in patients with primary biliary cholangitis (COBALT).2019.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02308111. Accessed February 20 2019"},{"key":"e_1_2_11_32_1","unstructured":"Clinicaltrials.gov.Study of OCA evaluating pharmacokinetics and safety in patients with PBC and hepatic impairment.2019.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03633227. Accessed February 20 2019."},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S64283"},{"issue":"1","key":"e_1_2_11_34_1","first-page":"31A","article-title":"Serum bilirubin within normal range is associated with an increasing risk of mortality in patients with primary biliary cholangitis regardless of ursodeoxycholic acid treatment","volume":"68","author":"Gordon S","year":"2018","journal-title":"Hepatology"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(16)01176-4"},{"issue":"3","key":"e_1_2_11_36_1","first-page":"164","article-title":"Evaluation of jaundice in adults","volume":"95","author":"Fargo MV","year":"2017","journal-title":"Am Fam Physician"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14429","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.14429","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14429","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T19:37:20Z","timestamp":1694029040000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.14429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,24]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/liv.14429"],"URL":"https:\/\/doi.org\/10.1111\/liv.14429","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,24]]},"assertion":[{"value":"2019-11-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}