{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:21:52Z","timestamp":1790709712678,"version":"4.1.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"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":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    There is growing interest in, but limited data about, intestinal bile acid transport inhibitors as treatment for cholestatic liver disease. The current analyses combine two similar randomized placebo\u2010controlled trials with subsequent extension phases investigating the impact of maralixibat in children with severe cholestasis secondary to Alagille Syndrome (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a057). The primary outcomes were measures of pruritus (ItchRO[Obs]) and clinician scratch scale (CSS), both increasing in severity from 0 to 4) and quality of life (QoL) (Parent PedsQL and Multidimensional Fatigue Scale module [MFS] scaled 0\u2013100 with increased QoL) at week 48 of the extension phase relative to the baseline of the placebo\u2010controlled trials (week 13). Secondary assessments included other clinical and biochemical parameters assessed in participants at week 72 or end of treatment (after week 48). At week 48, statistically and clinically significant least square mean (95% CI) improvements in pruritus and QoL were observed (ItchRO[Obs] \u22121.59 [\u22121.81, \u22121.36], CSS \u22121.36 [\u22121.67, \u22121.05], PedsQL +10.17 [4.48, 15.86], and multidimension fatigue [MFS] +13.97 [7.85, 20.08]). At week 48, serum bile acids, platelet count, and cholesterol decreased, whereas alanine aminotransferase (ALT) increased and total bilirubin (TB) and albumin were stable. Changes were durable at week 72 and end of treatment. There were no deaths; 2 participants underwent liver transplantation. Study drug was discontinued in 9 participants after treatment\u2010emergent adverse events, 6 of which were events of increased ALT or TB.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Maralixibat administration was associated with marked improvement in pruritus and QoL. Interpretation of these findings is complicated by the complex natural history of severe cholestasis in Alagille syndrome.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1992","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T01:38:40Z","timestamp":1654652320000},"page":"1922-1933","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":37,"title":["Impact of long\u2010term administration of maralixibat on children with cholestasis secondary to Alagille syndrome"],"prefix":"10.1097","volume":"6","author":[{"given":"Benjamin L.","family":"Shneider","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,Baylor College of Medicine and Texas Children's Hospital,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Spino","sequence":"additional","affiliation":[{"name":"University of Michigan,Ann Arbor,Michigan,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binita M.","family":"Kamath","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children,Toronto,Ontario,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Magee","sequence":"additional","affiliation":[{"name":"University of Michigan,Ann Arbor,Michigan,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalinda V.","family":"Ignacio","sequence":"additional","affiliation":[{"name":"University of Michigan,Ann Arbor,Michigan,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suiyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"University of Michigan,Ann Arbor,Michigan,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Horslen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Seattle Children's Hospital,University of Washington School of Medicine,Seattle,Washington,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean P.","family":"Molleston","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,Riley Hospital for Children,Indiana University,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Miethke","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,University of Cincinnati,Cincinnati,Ohio,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-7703","authenticated-orcid":false,"given":"Rohit","family":"Kohli","sequence":"additional","affiliation":[{"name":"Keck School of Medicine,University of Southern California,Los Angeles,California,USA"},{"name":"Liver Transplant Program,Children's Hospital\u2010Los Angeles,Los Angeles,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,Baylor College of Medicine and Texas Children's Hospital,Houston,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Kyle","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,University of Utah,Salt Lake City,Utah,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Loomes","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,The Children's Hospital of Philadelphia and Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania,Philadelphia,Pennsylvania,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul J.","family":"Karpen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,Children's Healthcare of Atlanta and Emory University School of Medicine,Atlanta,Georgia,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\u2010Gastroenterology, Hepatology, and Nutrition,University of Colorado School of Medicine and Children's Hospital Colorado,Aurora,Colorado,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,University of California, San Francisco,San Francisco,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Squires","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition,Department of Pediatrics,University of Pittsburgh, School of Medicine and Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center,Pittsburgh,Pennsylvania,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Child Health,The Pediatric Liver Center,King's College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Rajwal","sequence":"additional","affiliation":[{"name":"Children's Liver & GI Unit,The Leeds Hospital,Leeds,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre","family":"Kelly","sequence":"additional","affiliation":[{"name":"Liver Unit,Birmingham Women's & Children's Hospital,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Sokol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,University of California, San Francisco,San Francisco,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Child Health,The Pediatric Liver Center,King's College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for ChiLDReN and UK IMAGO\/IMAGINE 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