Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3

Autores
Frider, Bernardo; Castillo, Amalia Inés; Gordo Gilart, Raquel; Bruno, Andres; Amante, Marcelo; Alvarez, Luis; Mathet, Veronica Lidia
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction. Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a severe liver disorder associated with inherited dysfunction of multidrug resistance protein 3 (MDR3/ABCB4), which functions as a phospholipid floppase, translocating phosphatidylcholine from the inner to the outer hemileaflet of the canalicular membrane of hepatocytes. MDR3 deficiency results in a disbalanced bile which may damage the luminal membrane of cells of the hepatobiliary system. We evaluated clinical, biochemical and histological improvement in a genetically proven PFIC-3 patient after long-term ursodeoxycholic acid (UDCA) administration. Material and methods. A PFIC-3 patient and a relative with cholestatic liver disease were studied. Hepatic MDR3 expression was analyzed by immunohistochemistry and ABCB4 mutations were identified. The effect of the mutations on MDR3 expression and subcellular localization was studied in vitro. Results. A 23-year-old man presented cholestasis with severe fibrosis and incomplete cirrhosis. Canalicular staining for MDR3 was faint. Sequence analysis of ABCB4 revealed two missense mutations that reduce drastically protein expression levels. After 9 years of treatment with UDCA disappearance of fibrosis and cirrhosis was achieved. Conclusion. These data indicate that fibrosis associated with MDR3 deficiency can be reversed by long-term treatment with UDCA, at least when there is residual expression of the protein.
Fil: Frider, Bernardo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Castillo, Amalia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Gordo Gilart, Raquel. Hospital Universitario La Paz; España
Fil: Bruno, Andres. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Amante, Marcelo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Alvarez, Luis. Hospital Universitario La Paz; España
Fil: Mathet, Veronica Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Materia
Pfic-3
Abcb4
Cholestasis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38782
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/38782
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3Frider, BernardoCastillo, Amalia InésGordo Gilart, RaquelBruno, AndresAmante, MarceloAlvarez, LuisMathet, Veronica LidiaPfic-3Abcb4Cholestasishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Introduction. Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a severe liver disorder associated with inherited dysfunction of multidrug resistance protein 3 (MDR3/ABCB4), which functions as a phospholipid floppase, translocating phosphatidylcholine from the inner to the outer hemileaflet of the canalicular membrane of hepatocytes. MDR3 deficiency results in a disbalanced bile which may damage the luminal membrane of cells of the hepatobiliary system. We evaluated clinical, biochemical and histological improvement in a genetically proven PFIC-3 patient after long-term ursodeoxycholic acid (UDCA) administration. Material and methods. A PFIC-3 patient and a relative with cholestatic liver disease were studied. Hepatic MDR3 expression was analyzed by immunohistochemistry and ABCB4 mutations were identified. The effect of the mutations on MDR3 expression and subcellular localization was studied in vitro. Results. A 23-year-old man presented cholestasis with severe fibrosis and incomplete cirrhosis. Canalicular staining for MDR3 was faint. Sequence analysis of ABCB4 revealed two missense mutations that reduce drastically protein expression levels. After 9 years of treatment with UDCA disappearance of fibrosis and cirrhosis was achieved. Conclusion. These data indicate that fibrosis associated with MDR3 deficiency can be reversed by long-term treatment with UDCA, at least when there is residual expression of the protein.Fil: Frider, Bernardo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Castillo, Amalia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Gordo Gilart, Raquel. Hospital Universitario La Paz; EspañaFil: Bruno, Andres. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Amante, Marcelo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Alvarez, Luis. Hospital Universitario La Paz; EspañaFil: Mathet, Veronica Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaMexican Association of Hepatology2015-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38782Frider, Bernardo; Castillo, Amalia Inés; Gordo Gilart, Raquel; Bruno, Andres; Amante, Marcelo; et al.; Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3; Mexican Association of Hepatology; Annals of Hepatology; 14; 5; 10-2015; 745-7511665-2681CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://annalsofhepatology.publisherspanel.com/resources/html/article/details?id=127509&language=eninfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:08Zoai:ri.conicet.gov.ar:11336/38782instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:59:09.011CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3
title Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3
spellingShingle Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3
Frider, Bernardo
Pfic-3
Abcb4
Cholestasis
title_short Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3
title_full Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3
title_fullStr Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3
title_full_unstemmed Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3
title_sort Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3
dc.creator.none.fl_str_mv Frider, Bernardo
Castillo, Amalia Inés
Gordo Gilart, Raquel
Bruno, Andres
Amante, Marcelo
Alvarez, Luis
Mathet, Veronica Lidia
author Frider, Bernardo
author_facet Frider, Bernardo
Castillo, Amalia Inés
Gordo Gilart, Raquel
Bruno, Andres
Amante, Marcelo
Alvarez, Luis
Mathet, Veronica Lidia
author_role author
author2 Castillo, Amalia Inés
Gordo Gilart, Raquel
Bruno, Andres
Amante, Marcelo
Alvarez, Luis
Mathet, Veronica Lidia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Pfic-3
Abcb4
Cholestasis
topic Pfic-3
Abcb4
Cholestasis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Introduction. Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a severe liver disorder associated with inherited dysfunction of multidrug resistance protein 3 (MDR3/ABCB4), which functions as a phospholipid floppase, translocating phosphatidylcholine from the inner to the outer hemileaflet of the canalicular membrane of hepatocytes. MDR3 deficiency results in a disbalanced bile which may damage the luminal membrane of cells of the hepatobiliary system. We evaluated clinical, biochemical and histological improvement in a genetically proven PFIC-3 patient after long-term ursodeoxycholic acid (UDCA) administration. Material and methods. A PFIC-3 patient and a relative with cholestatic liver disease were studied. Hepatic MDR3 expression was analyzed by immunohistochemistry and ABCB4 mutations were identified. The effect of the mutations on MDR3 expression and subcellular localization was studied in vitro. Results. A 23-year-old man presented cholestasis with severe fibrosis and incomplete cirrhosis. Canalicular staining for MDR3 was faint. Sequence analysis of ABCB4 revealed two missense mutations that reduce drastically protein expression levels. After 9 years of treatment with UDCA disappearance of fibrosis and cirrhosis was achieved. Conclusion. These data indicate that fibrosis associated with MDR3 deficiency can be reversed by long-term treatment with UDCA, at least when there is residual expression of the protein.
Fil: Frider, Bernardo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Castillo, Amalia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Gordo Gilart, Raquel. Hospital Universitario La Paz; España
Fil: Bruno, Andres. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Amante, Marcelo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Alvarez, Luis. Hospital Universitario La Paz; España
Fil: Mathet, Veronica Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
description Introduction. Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a severe liver disorder associated with inherited dysfunction of multidrug resistance protein 3 (MDR3/ABCB4), which functions as a phospholipid floppase, translocating phosphatidylcholine from the inner to the outer hemileaflet of the canalicular membrane of hepatocytes. MDR3 deficiency results in a disbalanced bile which may damage the luminal membrane of cells of the hepatobiliary system. We evaluated clinical, biochemical and histological improvement in a genetically proven PFIC-3 patient after long-term ursodeoxycholic acid (UDCA) administration. Material and methods. A PFIC-3 patient and a relative with cholestatic liver disease were studied. Hepatic MDR3 expression was analyzed by immunohistochemistry and ABCB4 mutations were identified. The effect of the mutations on MDR3 expression and subcellular localization was studied in vitro. Results. A 23-year-old man presented cholestasis with severe fibrosis and incomplete cirrhosis. Canalicular staining for MDR3 was faint. Sequence analysis of ABCB4 revealed two missense mutations that reduce drastically protein expression levels. After 9 years of treatment with UDCA disappearance of fibrosis and cirrhosis was achieved. Conclusion. These data indicate that fibrosis associated with MDR3 deficiency can be reversed by long-term treatment with UDCA, at least when there is residual expression of the protein.
publishDate 2015
dc.date.none.fl_str_mv 2015-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/38782
Frider, Bernardo; Castillo, Amalia Inés; Gordo Gilart, Raquel; Bruno, Andres; Amante, Marcelo; et al.; Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3; Mexican Association of Hepatology; Annals of Hepatology; 14; 5; 10-2015; 745-751
1665-2681
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38782
identifier_str_mv Frider, Bernardo; Castillo, Amalia Inés; Gordo Gilart, Raquel; Bruno, Andres; Amante, Marcelo; et al.; Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3; Mexican Association of Hepatology; Annals of Hepatology; 14; 5; 10-2015; 745-751
1665-2681
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://annalsofhepatology.publisherspanel.com/resources/html/article/details?id=127509&language=en
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Mexican Association of Hepatology
publisher.none.fl_str_mv Mexican Association of Hepatology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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