{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:45:41Z","timestamp":1789422341781,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T00:00:00Z","timestamp":1520812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81361128006"],"award-info":[{"award-number":["81361128006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570468"],"award-info":[{"award-number":["81570468"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201606100226"],"award-info":[{"award-number":["201606100226"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2018,9]]},"abstract":"Abstract<\/jats:title>Background & Aims<\/jats:title>Genetic defects causing dysfunction in bile salt export pump (BSEP<\/jats:styled-content>\/ABCB<\/jats:styled-content>11<\/jats:italic>) lead to liver diseases. ABCB<\/jats:styled-content>11<\/jats:italic> mutations alter the bile acid metabolome. We asked whether profiling plasma bile acids could reveal compensatory mechanisms and track genetic and clinical status.<\/jats:p><\/jats:sec>Methods<\/jats:title>We compared plasma bile acids in 17 ABCB<\/jats:styled-content>11<\/jats:italic>\u2010mutated patients, 35 healthy controls and 12 genetically undiagnosed cholestasis patients by ultra\u2010high\u2010performance liquid chromatography\/multiple\u2010reaction monitoring\u2010mass spectrometry (UPLC<\/jats:styled-content>\/MRM<\/jats:styled-content>\u2010MS<\/jats:styled-content>). We developed an index to rank bile acid hydrophobicity, and thus toxicity, based on LC<\/jats:styled-content> retention times. We recruited 42 genetically diagnosed hereditary cholestasis patients, of whom 12 were presumed to have impaired BSEP<\/jats:styled-content> function but carried mutations in genes other than ABCB<\/jats:styled-content>11<\/jats:italic>, and 8 healthy controls, for further verification.<\/jats:p><\/jats:sec>Results<\/jats:title>The overall hydrophobicity indices of total bile acids in both the ABCB<\/jats:styled-content>11<\/jats:italic>\u2010mutated group (11.89\u00a0\u00b1\u00a01.07\u00a0min) and the undiagnosed cholestasis group (11.46\u00a0\u00b1\u00a01.07\u00a0min) were lower than those of healthy controls (13.69\u00a0\u00b1\u00a00.77\u00a0min) (both p\u00a0<\u00a00.005). This was owing to increased bile acid modifications. Secondary bile acids were detected in patients without BSEP<\/jats:styled-content> expression, suggesting biliary bile acid secretion through alternative routes. A diagnostic panel comprising lithocholic acid (LCA<\/jats:styled-content>), tauro\u2010LCA<\/jats:styled-content>, glyco\u2010LCA<\/jats:styled-content> and hyocholic acid was identified that could differentiate the ABCB<\/jats:styled-content>11<\/jats:italic>\u2010mutated cohort from healthy controls and undiagnosed cholestasis patients (AUC<\/jats:styled-content>=0.946, p\u00a0<\u00a00.0001) and, in non\u2010ABCB<\/jats:styled-content>11<\/jats:italic>\u2010mutated cholestasis patients, could distinguish BSEP<\/jats:styled-content> dysfunction from normal BSEP<\/jats:styled-content> function (9\/12 vs 0\/38, p\u00a0<\u00a00.0000001).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Profiling of plasma bile acids has provided insights into cholestasis alleviation and may be useful for the clinical management of cholestatic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13714","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T16:06:43Z","timestamp":1518019603000},"page":"1676-1685","source":"Crossref","is-referenced-by-count":20,"title":["Comprehensive bile acid profiling in hereditary intrahepatic cholestasis: Genetic and clinical correlations"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0858-2151","authenticated-orcid":false,"given":"Teng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics Jinshan Hospital of Fudan University Shanghai China"},{"name":"BC Cancer Agency Vancouver BC Canada"},{"name":"University of Victoria\u2212Genome BC Proteomics Centre University of Victoria Victoria BC Canada"},{"name":"Department of Pediatrics Shanghai Medical College Fudan University Shanghai China"},{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai 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Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Yan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jinshan Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-4360","authenticated-orcid":false,"given":"Li\u2010Ting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shanghai Medical College Fudan University Shanghai China"},{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-9873","authenticated-orcid":false,"given":"Neng\u2010Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jinshan Hospital of Fudan University Shanghai 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