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Recent developments in etiology and disease modeling of biliary atresia: a narrative review

Biliary atresia (BA) is a rare but severe fibroinflammatory disease of the extrahepatic and the intrahepatic bile ducts. Without prompt interventions, BA has fatal outcomes and is the most common indicator for pediatric liver transplantation (LTx). While the mainstay of treatment involves surgically...

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Autores principales: Malik, Astha, Thanekar, Unmesha, Mourya, Reena, Shivakumar, Pranavkumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891552/
https://www.ncbi.nlm.nih.gov/pubmed/33615212
http://dx.doi.org/10.21037/dmr-20-97
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author Malik, Astha
Thanekar, Unmesha
Mourya, Reena
Shivakumar, Pranavkumar
author_facet Malik, Astha
Thanekar, Unmesha
Mourya, Reena
Shivakumar, Pranavkumar
author_sort Malik, Astha
collection PubMed
description Biliary atresia (BA) is a rare but severe fibroinflammatory disease of the extrahepatic and the intrahepatic bile ducts. Without prompt interventions, BA has fatal outcomes and is the most common indicator for pediatric liver transplantation (LTx). While the mainstay of treatment involves surgically correcting the extrahepatic biliary obstruction via Kasai hepato-portoenterostomy (KHPE), activation of a multitude of biological pathways and yet-to-be-determined etiology in BA continue to foster liver inflammation, cirrhosis and need for LTx. However, important caveats still exist in our understandings of the biliary pathophysiology, the rapidity of liver fibrosis and progression to liver failure, largely due to limited knowledge of the triggers of biliary injury and the inability to accurately model human BA. Although inconclusive, a large body of existing literature points to a potential viral infection in the early peri- or postnatal period as triggers of epithelial injury that perpetuates the downstream biliary disease. Further confounding this issue, are the lack of in-vivo and in-vitro models to efficiently recapitulate the cardinal features of BA, primarily liver fibrosis. To overcome these barriers in BA research, new directions in recent years have enabled (I) identification of additional triggers of biliary injury linked mostly to environmental toxins, (II) development of models to investigate liver fibrogenesis, and (III) translational research using patient-derived organoids. Here, we discuss recent advances that undoubtedly will stimulate future efforts investigating these new and exciting avenues towards mechanistic and drug discovery efforts and disease-preventive measures. The implications of these emerging scientific investigations and disease modeling in severe fibrosing cholangiopathies like BA are enormous and contribute substantially in our understandings of this rare but deadly disease. These findings are also expected to facilitate expeditious identification of translationally targetable pathways and bring us one step closer in treating an infant with BA, a population highly vulnerable to life-long liver related complications.
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spelling pubmed-78915522021-02-18 Recent developments in etiology and disease modeling of biliary atresia: a narrative review Malik, Astha Thanekar, Unmesha Mourya, Reena Shivakumar, Pranavkumar Dig Med Res Article Biliary atresia (BA) is a rare but severe fibroinflammatory disease of the extrahepatic and the intrahepatic bile ducts. Without prompt interventions, BA has fatal outcomes and is the most common indicator for pediatric liver transplantation (LTx). While the mainstay of treatment involves surgically correcting the extrahepatic biliary obstruction via Kasai hepato-portoenterostomy (KHPE), activation of a multitude of biological pathways and yet-to-be-determined etiology in BA continue to foster liver inflammation, cirrhosis and need for LTx. However, important caveats still exist in our understandings of the biliary pathophysiology, the rapidity of liver fibrosis and progression to liver failure, largely due to limited knowledge of the triggers of biliary injury and the inability to accurately model human BA. Although inconclusive, a large body of existing literature points to a potential viral infection in the early peri- or postnatal period as triggers of epithelial injury that perpetuates the downstream biliary disease. Further confounding this issue, are the lack of in-vivo and in-vitro models to efficiently recapitulate the cardinal features of BA, primarily liver fibrosis. To overcome these barriers in BA research, new directions in recent years have enabled (I) identification of additional triggers of biliary injury linked mostly to environmental toxins, (II) development of models to investigate liver fibrogenesis, and (III) translational research using patient-derived organoids. Here, we discuss recent advances that undoubtedly will stimulate future efforts investigating these new and exciting avenues towards mechanistic and drug discovery efforts and disease-preventive measures. The implications of these emerging scientific investigations and disease modeling in severe fibrosing cholangiopathies like BA are enormous and contribute substantially in our understandings of this rare but deadly disease. These findings are also expected to facilitate expeditious identification of translationally targetable pathways and bring us one step closer in treating an infant with BA, a population highly vulnerable to life-long liver related complications. 2020-12 /pmc/articles/PMC7891552/ /pubmed/33615212 http://dx.doi.org/10.21037/dmr-20-97 Text en Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Article
Malik, Astha
Thanekar, Unmesha
Mourya, Reena
Shivakumar, Pranavkumar
Recent developments in etiology and disease modeling of biliary atresia: a narrative review
title Recent developments in etiology and disease modeling of biliary atresia: a narrative review
title_full Recent developments in etiology and disease modeling of biliary atresia: a narrative review
title_fullStr Recent developments in etiology and disease modeling of biliary atresia: a narrative review
title_full_unstemmed Recent developments in etiology and disease modeling of biliary atresia: a narrative review
title_short Recent developments in etiology and disease modeling of biliary atresia: a narrative review
title_sort recent developments in etiology and disease modeling of biliary atresia: a narrative review
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891552/
https://www.ncbi.nlm.nih.gov/pubmed/33615212
http://dx.doi.org/10.21037/dmr-20-97
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