{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:58:59Z","timestamp":1789556339115,"version":"build-2803163510"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T00:00:00Z","timestamp":1567036800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>\n                    Ursodeoxycholic acid (UDCA) is commonly used to treat several liver disorders in adults and children, including primary sclerosing cholangitis (PSC) for which it is not U.S. Food and Drug Administration approved. UDCA treatment has an uncertain impact on disease outcomes and has been reported in high doses to be associated with worse outcome in adults with PSC. In this context, controlled withdrawal and reintroduction of UDCA in children with PSC were studied. Prior to study initiation, participants were required to have alanine aminotransferase (ALT) and gamma\u2010glutamyl transpeptidase (GGT) &lt;2 times the upper limit of normal on stable UDCA dosing. The study included four phases: I (stable dosing), II (50% UDCA reduction), III (UDCA discontinuation), IV (UDCA reintroduction), with a primary endpoint of change in ALT and GGT between phases I and III. We enrolled 27 participants (22 completed) between March 2011 and June 2016. Changes in mean ALT and GGT between phases I and III were ALT, +29.5\u00a0IU\/L (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.105) and GGT, +60.4\u00a0IU\/L (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.003). In 7 participants, ALT and GGT \u226429\u00a0IU\/L did not rise above 29\u00a0IU\/L (null response group). Eight participants had increases of ALT or GGT\u00a0&gt;100\u00a0IU\/L (flare group). None developed elevated bilirubin. All flares responded to UDCA reinstitution. Serum GGT, interleukin\u20108, and tumor necrosis factor \u03b1 levels were higher in the flare group at baseline. Liver biochemistries increased in children with PSC during controlled UDCA withdrawal; one third increased above 100\u00a0IU\/L and one third remained normal during UDCA withdrawal.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : The impact of prolonged UDCA use in childhood PSC and the significance of a biochemical flare are unclear. Further studies of the natural history and treatment of pediatric PSC and UDCA use are needed.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1421","type":"journal-article","created":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T09:57:14Z","timestamp":1567072634000},"page":"1482-1495","source":"Crossref","is-referenced-by-count":25,"title":["A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis"],"prefix":"10.1097","volume":"3","author":[{"given":"Dennis D.","family":"Black","sequence":"first","affiliation":[{"name":"Pediatrics,University of Tennessee Health Science Center,Memphis,TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Mack","sequence":"additional","affiliation":[{"name":"Pediatrics,University of Colorado School of 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Corporation,Rockville,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Emmes Corporation,Rockville,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estella","family":"Alonso","sequence":"additional","affiliation":[{"name":"Pediatrics,Northwestern University College of Medicine,Chicago,IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronen","family":"Arnon","sequence":"additional","affiliation":[{"name":"Pediatrics,Mount Sinai Icahn School of Medicine,New York,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Bulut","sequence":"additional","affiliation":[{"name":"Pediatrics,Phoenix Children's Hospital,Phoenix,AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul","family":"Karpen","sequence":"additional","affiliation":[{"name":"Pediatrics,Emory University School of Medicine,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan\u2010Hao","family":"Lin","sequence":"additional","affiliation":[{"name":"Pediatrics,Keck School of Medicine of University of Southern California,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Pediatrics,School of Medicine,University of California, San Francisco,San Francisco,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Ryan","sequence":"additional","affiliation":[{"name":"Pediatrics,Children's Hospital of Philadelphia,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Squires","sequence":"additional","affiliation":[{"name":"Pediatrics,University of Pittsburgh School of Medicine,Pittsburgh,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8227-2004","authenticated-orcid":false,"given":"Pamela","family":"Valentino","sequence":"additional","affiliation":[{"name":"Pediatrics,Yale School of Medicine,New Haven,CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah H.","family":"Elsea","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Shneider","sequence":"additional","affiliation":[{"name":"Pediatrics,Baylor College of Medicine,Houston,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,8,29]]},"reference":[{"key":"hep41421-bib-0001-20240114","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/hep.21337","article-title":"Primary sclerosing cholangitis: summary of a 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