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

Autor: Veronica Lidia Mathet, Luis Alvarez, Amalia Inés Castillo, Marcelo Amante, Bernardo Frider, Raquel Gordo-Gilart, Andrés Bruno
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Liver Cirrhosis
Male
Pathology
Cholagogues and Choleretics
Cirrhosis
Time Factors
DNA Mutational Analysis
Specialties of internal medicine
ATP-binding cassette transporter
Severity of Illness Index
Liver disorder
Madin Darby Canine Kidney Cells
Fibrosis
Abcb4
Cholestasis
Remission Induction
Ursodeoxycholic Acid
Progressive familial intrahepatic cholestasis
PFIC-3
General Medicine
ABCB4
purl.org/becyt/ford/3.1 [https]
Immunohistochemistry
Ursodeoxycholic acid
Medicina Básica
Phenotype
Treatment Outcome
RC581-951
Pfic-3
Elasticity Imaging Techniques
purl.org/becyt/ford/3 [https]
medicine.drug
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD
ATP Binding Cassette Transporter
Subfamily B
Genética Humana
Mutation
Missense
Cholestasis
Intrahepatic
Transfection
Young Adult
Dogs
medicine
Animals
Humans
Genetic Predisposition to Disease
Hepatology
business.industry
medicine.disease
HEK293 Cells
business
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Annals of Hepatology, Vol 14, Iss 5, Pp 745-751 (2015)
Popis: 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
Databáze: OpenAIRE
Externí odkaz: