{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:01:07Z","timestamp":1792839667484,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018262","name":"Intercept Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018262","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Fibrosis stage is a strong predictor of nonalcoholic steatohepatitis (NASH) outcomes. Two blinded studies evaluated the pharmacokinetics, pharmacodynamics and safety of obeticholic acid (OCA) in subjects with staged NASH fibrosis or cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Study 747\u2010117 randomized 51 subjects with NASH (fibrosis stages F1\u2013F4) to daily placebo, OCA 10 or OCA 25\u2009mg (1:2:2) for 85\u2009days. Study 747\u2010118 randomized 24 subjects with NASH cirrhosis (F4; Child\u2010Pugh [CP]\u2010A) and normal liver control subjects matched for similar body weight to daily OCA 10 or OCA 25\u2009mg (1:1) for 28\u2009days. Individual and combined study data were analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No severe or serious adverse events (AEs) or AEs leading to discontinuation or death occurred. Pruritus was the most frequent AE. Plasma OCA exposure (dose\u2010normalized area under the curve) increased with fibrosis stage but was a relatively poor predictor of hepatic OCA exposure (primary site of action), which remained constant across fibrosis stages F1\u2013F3 and increased 1.8\u2010fold compared with F1 in subjects with cirrhosis due to NASH. Both cohorts showed robust changes in farnesoid X receptor activation markers with OCA treatment and marked decreases in alanine transaminase, aspartate transaminase and gamma\u2010glutamyltransferase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite higher drug exposures in subjects with NASH cirrhosis, short\u2010term daily treatment with OCA 10 or 25\u2009mg was generally safe and well tolerated in subjects with NASH fibrosis or NASH CP\u2010A cirrhosis. Both cohorts experienced improvements in nonhistologic pharmacodynamic markers consistent with previously conducted OCA phase 2 and phase 3 studies in NASH fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15816","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T09:15:18Z","timestamp":1706692518000},"page":"966-978","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Safety, pharmacokinetics and pharmacodynamics of obeticholic acid in subjects with fibrosis or cirrhosis from NASH"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9872-2391","authenticated-orcid":false,"given":"Naim","family":"Alkhouri","sequence":"first","affiliation":[{"name":"The Texas Liver Institute University of Texas Health San Antonio  San Antonio Texas USA"},{"name":"Arizona Liver Health  Chandler Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"LaCerte","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Edwards","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1503-1569","authenticated-orcid":false,"given":"Fred","family":"Poordad","sequence":"additional","affiliation":[{"name":"The Texas Liver Institute University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-224X","authenticated-orcid":false,"given":"Eric","family":"Lawitz","sequence":"additional","affiliation":[{"name":"The Texas Liver Institute University of Texas Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lois","family":"Lee","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Karan","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta","family":"Sawhney","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  Morristown New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Erickson","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"MacConell","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna","family":"Zaru","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfen","family":"Chen","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Campagna","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1586\/egh.09.32"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70506-8"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29367"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(14)61933-4"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(19)33041-7"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.05.042"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.329"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2012.05.012"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509840"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0616-x"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.07.014"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(96)06305-x"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e3282f4710a"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12468"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i41.11597"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12421"},{"key":"e_1_2_16_19_1","unstructured":"Obeticholic Acid (Ocaliva) [Package Insert]. 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