{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:09:18Z","timestamp":1792001358463,"version":"4.4.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":427,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Microvillous inclusion disease (MVID) is a congenital disorder of the enterocyte related to mutations in the<\/jats:bold>\n                      <jats:bold>MYO5B<\/jats:bold>\n                      <jats:bold>gene, leading to intractable diarrhea often necessitating intestinal transplantation (ITx). Among our cohort of 28 MVID patients, 8 developed a cholestatic liver disease akin to progressive familial intrahepatic cholestasis (PFIC). Our aim was to investigate the mechanisms by which MYO5B mutations affect hepatic biliary function and lead to cholestasis in MVID patients. Clinical and biological features and outcome were reviewed. Pretransplant liver biopsies were analyzed by immunostaining and electron microscopy. Cholestasis occurred before (n = 5) or after (n = 3) ITx and was characterized by intermittent jaundice, intractable pruritus, increased serum bile acid (BA) levels, and normal gamma-glutamyl transpeptidase activity. Liver histology showed canalicular cholestasis, mild-to-moderate fibrosis, and ultrastructural abnormalities of bile canaliculi. Portal fibrosis progressed in 5 patients. No mutation in<\/jats:bold>\n                      <jats:bold>ABCB11\/BSEP<\/jats:bold>\n                      <jats:bold>or<\/jats:bold>\n                      <jats:bold>ATP8B1\/FIC1<\/jats:bold>\n                      <jats:bold>genes were identified. Immunohistochemical studies demonstrated abnormal cytoplasmic distribution of MYO5B, RAB11A, and BSEP in hepatocytes. Interruption of enterohepatic BA cycling after partial external biliary diversion or graft removal proved the most effective to ensure long-term remission.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion :<\/jats:title>\n                    <jats:p>\n                      <jats:bold>MVID patients are at risk of developing a PFIC-like liver disease that may hamper outcome after ITx. Our results suggest that cholestasis in MVID patients results from (1) impairment of the MYO5B\/RAB11A apical recycling endosome pathway in hepatocytes, (2) altered targeting of BSEP to the canalicular membrane, and (3) increased ileal BA absorption. Because cholestasis worsens after ITx, indication of a combined liver ITx should be discussed in MVID patients with severe cholestasis. Future studies will need to address more specifically the effect of<\/jats:bold>\n                      <jats:bold>MYO5B<\/jats:bold>\n                      <jats:bold>dysfunction in BA homeostasis. (Hepatology 2014;60:301\u2013310)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.26974","type":"journal-article","created":{"date-parts":[[2013,12,21]],"date-time":"2013-12-21T00:36:50Z","timestamp":1387586210000},"page":"301-310","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":128,"title":["MYO5B and Bile Salt Export Pump Contribute to Cholestatic Liver Disorder in Microvillous Inclusion Disease"],"prefix":"10.1097","volume":"60","author":[{"given":"Muriel","family":"Girard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lacaille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Verkarre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Mategot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Feldmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Grodet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Sauvat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Irtan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Davit-Spraul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Jacquemin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ruemmele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Rainteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Goulet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Colomb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Chardot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Henrion-Caude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Debray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-35-20250207","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1750-1172-1-22","article-title":"Microvillous inclusion disease (microvillous atrophy).","volume":"1","author":"Ruemmele","year":"2006","journal-title":"Orphanet J Rare Dis"},{"key":"R2-35-20250207","first-page":"239246","article-title":"The constitutive exocytotic pathway in microvillous atrophy.","volume":"17","author":"Phillips","year":"1993","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R3-35-20250207","doi-asserted-by":"crossref","first-page":"11631165","DOI":"10.1038\/ng.225","article-title":"MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity.","volume":"40","author":"Muller","year":"2008","journal-title":"Nat Genet"},{"key":"R4-35-20250207","first-page":"7683","article-title":"Microvillus inclusion disease: a genetic defect affecting apical membrane protein traffic in intestinal epithelium.","volume":"1","author":"Ameen","year":"2000","journal-title":"Traffic Cph Den"},{"key":"R5-35-20250207","doi-asserted-by":"crossref","first-page":"1508715092","DOI":"10.1073\/pnas.0503702102","article-title":"Rab11a and myosin Vb are required for bile canalicular formation in WIFB9 cells.","volume":"102","author":"Wakabayashi","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R6-35-20250207","first-page":"715723","article-title":"Interactions of myosin vb with rab11 family members and cargoes traversing the plasma membrane recycling system.","volume":"403","author":"Lapierre","year":"2005","journal-title":"Methods Enzymol"},{"key":"R7-35-20250207","doi-asserted-by":"crossref","first-page":"34853496","DOI":"10.1091\/mbc.e03-10-0737","article-title":"Intracellular trafficking of bile salt export pump (ABCB11) in polarized hepatic cells: constitutive cycling between the canalicular membrane and rab11positive endosomes.","volume":"15","author":"Wakabayashi","year":"2004","journal-title":"Mol Biol Cell"},{"key":"R8-35-20250207","doi-asserted-by":"crossref","first-page":"307313","DOI":"10.1097\/MPG.0b013e3181eea177","article-title":"Functional characterization of mutations in the myosin Vb gene associated with microvillus inclusion disease.","volume":"52","author":"Szperl","year":"2011","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R9-35-20250207","doi-asserted-by":"crossref","first-page":"491498","DOI":"10.1097\/MPG.0b013e3182353773","article-title":"MYO5B mutations in patients with microvillus inclusion disease presenting with transient renal Fanconi syndrome.","volume":"54","author":"Golachowska","year":"2012","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R10-35-20250207","doi-asserted-by":"crossref","first-page":"460465","DOI":"10.1097\/MPG.0b013e3181fb4559","article-title":"Microvillous inclusion disease: how to improve the prognosis of a severe congenital enterocyte disorder.","volume":"52","author":"Halac","year":"2011","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R11-35-20250207","doi-asserted-by":"crossref","first-page":"135145","DOI":"10.1016\/j.jchromb.2012.05.015","article-title":"Bile acid profiling in human biological samples: comparison of extraction procedures and application to normal and cholestatic patients.","volume":"899","author":"Humbert","year":"2012","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"R12-35-20250207","doi-asserted-by":"crossref","first-page":"289293","DOI":"10.1002\/hep.510240201","article-title":"An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group.","volume":"24","author":"Bedossa","year":"1996","journal-title":"Hepatology"},{"key":"R13-35-20250207","doi-asserted-by":"crossref","first-page":"729738","DOI":"10.1002\/hep.26360","article-title":"Persistent abnormal liver fibrosis after weaning off parenteral nutrition in pediatric intestinal failure.","volume":"58","author":"Mutanen","year":"2013","journal-title":"Hepatology"},{"key":"R14-35-20250207","first-page":"16451655","article-title":"ATP8B1 and ABCB11 analysis in 62 children with normal gammaglutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history.","volume":"51","author":"DavitSpraul","year":"2010","journal-title":"Hepatology"},{"key":"R15-35-20250207","doi-asserted-by":"crossref","first-page":"544551","DOI":"10.1002\/humu.21224","article-title":"Lossoffunction of MYO5B is the main cause of microvillus inclusion disease: 15 novel mutations and a CaCo2 RNAi cell model.","volume":"31","author":"Ruemmele","year":"2010","journal-title":"Hum Mutat"},{"key":"R16-35-20250207","first-page":"307311","article-title":"Surgical treatment of progressive familial intrahepatic cholestasis: comparison of partial external biliary diversion and ileal bypass.","volume":"13","author":"Kalicinski","year":"2003","journal-title":"Eur J Pediatr Surg Off J Austrian Assoc Pediatr Surg Al Z Fur Kinderchir"},{"key":"R17-35-20250207","doi-asserted-by":"crossref","first-page":"130136","DOI":"10.1016\/0016-5085(88)90301-0","article-title":"Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis.","volume":"95","author":"Whitington","year":"1988","journal-title":"Gastroenterology"},{"key":"R18-35-20250207","doi-asserted-by":"crossref","first-page":"6274","DOI":"10.1002\/hep.21214","article-title":"Interindividual variability of canalicular ATPbindingcassette (ABC)transporter expression in human liver.","volume":"44","author":"Meier","year":"2006","journal-title":"Hepatology"},{"key":"R19-35-20250207","doi-asserted-by":"crossref","first-page":"411425","DOI":"10.1517\/17425255.2011.557067","article-title":"Genetic variations of bile salt transporters as predisposing factors for druginduced cholestasis, intrahepatic cholestasis of pregnancy and therapeutic response of viral hepatitis.","volume":"7","author":"Stieger","year":"2011","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"R20-35-20250207","doi-asserted-by":"crossref","first-page":"9911004","DOI":"10.1242\/jcs.115.5.991","article-title":"Human myosinVc is a novel class V myosin expressed in epithelial cells.","volume":"115","author":"Rodriguez","year":"2002","journal-title":"J Cell Sci"},{"key":"R21-35-20250207","doi-asserted-by":"crossref","first-page":"155164","DOI":"10.1002\/hep.510260121","article-title":"Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease PFIC1 and Byler syndrome): evidence for heterogeneity.","volume":"26","author":"Bull","year":"1997","journal-title":"Hepatology"},{"key":"R22-35-20250207","doi-asserted-by":"crossref","first-page":"687696","DOI":"10.1097\/PAS.0b013e318212ec87","article-title":"Morphologic findings in progressive familial intrahepatic cholestasis 2 (PFIC2): correlation with genetic and immunohistochemical studies.","volume":"35","author":"Evason","year":"2011","journal-title":"Am J Surg Pathol"},{"key":"R23-35-20250207","first-page":"265271","article-title":"Liver ultrastructure in congenital atresia of the extrahepatic bile ducts.","volume":"14","author":"Arias","year":"1984","journal-title":"Acta Gastroenterol Latinoam"},{"key":"R24-35-20250207","doi-asserted-by":"crossref","first-page":"347353","DOI":"10.1097\/MPG.0b013e31802c6971","article-title":"Longterm outcome of children receiving home parenteral nutrition: a 20year singlecenter experience in 302 patients.","volume":"44","author":"Colomb","year":"2007","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R25-35-20250207","doi-asserted-by":"crossref","first-page":"735737","DOI":"10.3109\/0886022X.2013.780621","article-title":"Tacrolimusinduced severe cholestasis complicating renal transplantation.","volume":"35","author":"Yadav","year":"2013","journal-title":"Ren Fail"},{"key":"R26-35-20250207","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1471-230X-8-47","article-title":"Bile composition in Alagille Syndrome and PFIC patients having Partial External Biliary Diversion.","volume":"8","author":"Emerick","year":"2008","journal-title":"BMC Gastroenterol"},{"key":"R27-35-20250207","doi-asserted-by":"crossref","first-page":"303312","DOI":"10.1038\/ng.538","article-title":"Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization.","volume":"42","author":"Cullinane","year":"2010","journal-title":"Nat Genet"},{"key":"R28-35-20250207","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1124\/mol.108.045674","article-title":"Identification of regions required for apical membrane localization of human multidrug resistance protein 2.","volume":"74","author":"Bandler","year":"2008","journal-title":"Mol Pharmacol"},{"key":"R29-35-20250207","doi-asserted-by":"crossref","first-page":"2374123747","DOI":"10.1074\/jbc.M502767200","article-title":"Myosin II regulatory light chain is required for trafficking of bile salt export protein to the apical membrane in MadinDarby canine kidney cells.","volume":"280","author":"Chan","year":"2005","journal-title":"J Biol Chem"},{"key":"R30-35-20250207","doi-asserted-by":"crossref","first-page":"12391241","DOI":"10.1136\/gut.52.9.1239","article-title":"Inappropriate ileal conservation of bile acids in cholestatic liver disease: homeostasis gone awry.","volume":"52","author":"Hofmann","year":"2003","journal-title":"Gut"},{"key":"R31-35-20250207","doi-asserted-by":"crossref","first-page":"217225","DOI":"10.1016\/j.cmet.2005.09.001","article-title":"Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis.","volume":"2","author":"Inagaki","year":"2005","journal-title":"Cell Metab"},{"key":"R32-35-20250207","doi-asserted-by":"crossref","first-page":"501505","DOI":"10.1016\/j.jpedsurg.2011.08.010","article-title":"Normalization of serum bile acids after partial external biliary diversion indicates an excellent longterm outcome in children with progressive familial intrahepatic cholestasis.","volume":"47","author":"Schukfeh","year":"2012","journal-title":"J Pediatr Surg"},{"key":"R33-35-20250207","doi-asserted-by":"crossref","first-page":"12271234","DOI":"10.1016\/S0016-5085(03)01199-5","article-title":"Biliary diversion for progressive familial intrahepatic cholestasis: improved liver morphology and bile acid profile.","volume":"125","author":"Kurbegov","year":"2003","journal-title":"Gastroenterology"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.26974","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201407000-00035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T12:12:04Z","timestamp":1738930324000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201407000-00035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.26974","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718219747.793497312","asserted-by":"object"}]},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2014,7]]}}}