title: Prognostic roles of tetrahydroxy bile acids in infantile intrahepatic cholestasis.
abstract: Tetrahydroxy bile acids (THBAs) are hydrophilic and are present at minimal or undetectable levels in healthy human adults, but are present at high levels in bile salt export pump (abcb11)-knockout mice. The roles of THBAs in human cholestatic diseases are unclear. We aimed to investigate the presence of THBAs in patients with infantile intrahepatic cholestasis and its correlation with outcome. Urinary bile acids (BAs) were analyzed by GC-MS. Data were compared between good (n = 21) (disease-free before 1 year old) and poor prognosis groups (n = 19). Good prognosis patients had a higher urinary THBA proportion than poor prognosis patients [25.89% (3.45-76.73%) vs. 1.93% (0.05-48.90%)]. A urinary THBA proportion >7.23% predicted good prognosis with high sensitivity (95.24%), specificity (84.21%), and area under the curve (0.91) (P< 0.0001). A THBA proportion 7.23% was an independent factor for decreased transplant-free survival (hazard ratio = 7.16, confidence interval: 1.24-41.31,P= 0.028). Patients with a confirmedABCB11or tight junction protein 2 gene mutation (n = 7) had a minimally detectable THBA proportion (0.23-2.99% of total BAs). Three patients with anATP8B1mutation had an elevated THBA proportion (7.51-37.26%). In conclusion, in addition to disease entity as a major determinant of outcome, a high THBA level was associated with good outcome in the infantile intrahepatic cholestasis patients.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.|Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan.
authors.forename: Chee-Seng
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kimura
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jia-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.|Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.|Department of Medical Education and Bioethics, Graduate Institute of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Hsu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.|Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
authors.affiliation: Junshin Clinic Bile Acid Institute, Meguro-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nittono
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan hueyling@ntu.edu.tw.|Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.|Department of Medical Education and Bioethics, Graduate Institute of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics*; D001647:Bile Acids and Salts / Q000235:genetics / Q000652:urine*; D002780:Cholestasis, Intrahepatic / Q000235:genetics / Q000473:pathology / Q000652:urine*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011379:Prognosis; D062827:Zonula Occludens-2 Protein / Q000235:genetics*
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D062827:Zonula Occludens-2 Protein; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human
keywords: bile acid metabolism; bile salts; clinical studies; cytochrome P450; diseases; liver; progressive familial intrahepatic cholestasis