{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:12:44Z","timestamp":1789985564218,"version":"4.0.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T00:00:00Z","timestamp":1431388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T00:00:00Z","timestamp":1431388800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>\n                    We investigated predictors of clinical evolution in progressive familial intrahepatic cholestasis type 2 patients and how they relate to bile salt export pump (BSEP) expression and its (re)targeting. Our retrospective study included 22 children with progressive familial intrahepatic cholestasis type 2. Clinical, biochemical, and histological characteristics were reviewed on admittance and following treatment with either ursodeoxycholic acid alone (10 mg\/kg thrice daily, n\u2009=\u200919) or partial biliary diversion (n\u2009=\u20093). Immunostaining of BSEP was performed in 20 patients. Response to treatment was defined as normalization of pruritus, disappearance of jaundice, and alanine aminotransferase (ALT) levels &lt;1.5 times the upper limit of normal. Ten of 22 patients were responders, and paired biopsies were available in six.\n                    <jats:italic toggle=\"yes\">De novo<\/jats:italic>\n                    or retargeted canalicular expression of BSEP occurred in four of these six, two of whom exhibited baseline intracellular expression. Twelve of 22 were nonresponders and exhibited earlier onset of jaundice (&lt;9 months), neonatal cholestasis, and higher ALT levels. An ALT &gt;165 IU\/L produced 72% sensitivity and 55% specificity in predicting nonresponse. Seven patients were still responding at last follow\u2010up (median\u2009=\u200920 months, range 5\u201067 months). Three responders relapsed after 56, 72, and 82 months, respectively. Of nine surviving responders, median relapse\u2010free survival time was 72 months (95% confidence interval 48\u201096 months) and 5\u2010year relapse\u2010free survival was 75% (95% confidence interval 33\u2010100%). Intracellular BSEP at baseline was seen in six, of whom five were responders. Genetic analysis was performed in 17 of 22, confirming diagnosis in 13 (76%) and in four (24%) in whom only heterozygous mutation was identified.\n                    <jats:italic toggle=\"yes\">Conclusion: De novo<\/jats:italic>\n                    or retargeted canalicular expression of BSEP occurs in treatment responders; children with late\u2010onset presentation, lower ALT, and intracellular BSEP expression are likely to respond, at least transiently, to nontransplant treatment. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2015;62:198\u2010206)\n                  <\/jats:p>","DOI":"10.1002\/hep.27834","type":"journal-article","created":{"date-parts":[[2015,4,4]],"date-time":"2015-04-04T03:30:22Z","timestamp":1428118222000},"page":"198-206","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["Retargeting of bile salt export pump and favorable outcome in children with progressive familial intrahepatic cholestasis type 2"],"prefix":"10.1097","volume":"62","author":[{"given":"Sharat","family":"Varma","sequence":"first","affiliation":[{"name":"Service de Gastroent\u00e9rologie et H\u00e9patologie P\u00e9diatrique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Revencu","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique Humaine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Stephenne","sequence":"additional","affiliation":[{"name":"Service de Gastroent\u00e9rologie et H\u00e9patologie P\u00e9diatrique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Scheers","sequence":"additional","affiliation":[{"name":"Service de Gastroent\u00e9rologie et H\u00e9patologie P\u00e9diatrique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Smets","sequence":"additional","affiliation":[{"name":"Service de Gastroent\u00e9rologie et H\u00e9patologie P\u00e9diatrique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Beleza\u2010Meireles","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique Humaine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Reding","sequence":"additional","affiliation":[{"name":"Unit\u00e9s de Chirurgie P\u00e9diatrique,Universit\u00e9 Catholique de Louvain,Cliniques Universitaires St. Luc,Brussels,Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Roskams","sequence":"additional","affiliation":[{"name":"Katholiek Universiteit Leuven,University Hospital Gasthuisberg,Leuven,Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne M.","family":"Sokal","sequence":"additional","affiliation":[{"name":"Service de Gastroent\u00e9rologie et H\u00e9patologie P\u00e9diatrique"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,5,12]]},"reference":[{"key":"hep27834-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1172-4-1","article-title":"Progressive familial intrahepatic cholestasis","volume":"4","year":"2009","journal-title":"Orphanet J Rare 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