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Article: Beta-amyloid deposition around hepatic bile ducts is a novel pathobiological and diagnostic feature of biliary atresia

TitleBeta-amyloid deposition around hepatic bile ducts is a novel pathobiological and diagnostic feature of biliary atresia
Authors
KeywordsLiver disease
Bile duct
Cholangiopathy
Organoid
Amyloid
Issue Date2020
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
Journal of Hepatology, 2020, v. 73 n. 6, p. 1391-1403 How to Cite?
AbstractBackground and Aims: Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. In this study, we aimed to investigate the underlying pathogenesis and molecular signatures associated with BA. Methods: We combined organoid and transcriptomic analysis to gain new insights into BA pathobiology using patient samples and a mouse model of BA. Results: Liver organoids derived from patients with BA and a rhesus rotavirus A-infected mouse model of BA, exhibited aberrant morphology and disturbed apical-basal organization. Transcriptomic analysis of BA organoids revealed a shift from cholangiocyte to hepatocyte transcriptional signatures and altered beta-amyloid-related gene expression. Beta-amyloid accumulation was observed around the bile ducts in BA livers and exposure to beta-amyloid induced the aberrant morphology in control organoids. Conclusion: The novel observation that beta-amyloid accumulates around bile ducts in the livers of patients with BA has important pathobiological implications, as well as diagnostic potential. Lay summary: Biliary atresia is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. Using human and mouse 'liver mini-organs in the dish', we unexpectedly identified beta-amyloid deposition the main pathological feature of Alzheimer's disease and cerebral amyloid angiopathy - around bile ducts in livers from patients with biliary atresia. This finding reveals a novel pathogenic mechanism that could have important diagnostic and therapeutic implications. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.
DescriptionHybrid open access
Persistent Identifierhttp://hdl.handle.net/10722/295243
ISSN
2019 Impact Factor: 20.582
2015 SCImago Journal Rankings: 4.570
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorOttakandathil Babu, R-
dc.contributor.authorLui, VCH-
dc.contributor.authorChen, Y-
dc.contributor.authorYIU, RSW-
dc.contributor.authorYe, Y-
dc.contributor.authorNiu, B-
dc.contributor.authorWu, Z-
dc.contributor.authorZhang, R-
dc.contributor.authorYu, MON-
dc.contributor.authorChung, PHY-
dc.contributor.authorWong, KKY-
dc.contributor.authorXia, H-
dc.contributor.authorZhang, MQ-
dc.contributor.authorWang, B-
dc.contributor.authorLendahl, U-
dc.contributor.authorTam, PKH-
dc.date.accessioned2021-01-11T13:57:22Z-
dc.date.available2021-01-11T13:57:22Z-
dc.date.issued2020-
dc.identifier.citationJournal of Hepatology, 2020, v. 73 n. 6, p. 1391-1403-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/295243-
dc.descriptionHybrid open access-
dc.description.abstractBackground and Aims: Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. In this study, we aimed to investigate the underlying pathogenesis and molecular signatures associated with BA. Methods: We combined organoid and transcriptomic analysis to gain new insights into BA pathobiology using patient samples and a mouse model of BA. Results: Liver organoids derived from patients with BA and a rhesus rotavirus A-infected mouse model of BA, exhibited aberrant morphology and disturbed apical-basal organization. Transcriptomic analysis of BA organoids revealed a shift from cholangiocyte to hepatocyte transcriptional signatures and altered beta-amyloid-related gene expression. Beta-amyloid accumulation was observed around the bile ducts in BA livers and exposure to beta-amyloid induced the aberrant morphology in control organoids. Conclusion: The novel observation that beta-amyloid accumulates around bile ducts in the livers of patients with BA has important pathobiological implications, as well as diagnostic potential. Lay summary: Biliary atresia is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. Using human and mouse 'liver mini-organs in the dish', we unexpectedly identified beta-amyloid deposition the main pathological feature of Alzheimer's disease and cerebral amyloid angiopathy - around bile ducts in livers from patients with biliary atresia. This finding reveals a novel pathogenic mechanism that could have important diagnostic and therapeutic implications. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectLiver disease-
dc.subjectBile duct-
dc.subjectCholangiopathy-
dc.subjectOrganoid-
dc.subjectAmyloid-
dc.titleBeta-amyloid deposition around hepatic bile ducts is a novel pathobiological and diagnostic feature of biliary atresia-
dc.typeArticle-
dc.identifier.emailLui, VCH: vchlui@hku.hk-
dc.identifier.emailChen, Y: ychenc@hku.hk-
dc.identifier.emailWu, Z: hannawu@hku.hk-
dc.identifier.emailChung, PHY: chungphy@hku.hk-
dc.identifier.emailWong, KKY: kkywong@hku.hk-
dc.identifier.emailTam, PKH: paultam@hku.hk-
dc.identifier.authorityLui, VCH=rp00363-
dc.identifier.authorityChen, Y=rp01318-
dc.identifier.authorityChung, PHY=rp02002-
dc.identifier.authorityWong, KKY=rp01392-
dc.identifier.authorityTam, PKH=rp00060-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.jhep.2020.06.012-
dc.identifier.pmid32553668-
dc.identifier.hkuros320794-
dc.identifier.volume73-
dc.identifier.issue6-
dc.identifier.spage1391-
dc.identifier.epage1403-
dc.identifier.isiWOS:000590263100017-
dc.publisher.placeNetherlands-

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