| Journal: | Annals of hepatology |
| Database: | PERIÓDICA |
| System number: | 000391021 |
| ISSN: | 1665-2681 |
| Authors: | Frider, Bernardo1 Castillo, Amalia2 Gordo Gilart, Raquel3 Bruno, Andrés1 Amante, Marcelo1 Alvarez, Luis3 Mathet, Verónica2 |
| Institutions: | 1Hospital General de Agudos "Dr. Cosme Argerich", Servicio de Hepatología Clínica, Buenos Aires. Argentina 2Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires. Argentina 3Universidad Autónoma de Madrid, Hospital Universitario La Paz, Madrid. España |
| Year: | 2015 |
| Season: | Sep-Oct |
| Volumen: | 14 |
| Number: | 5 |
| Pages: | 745-751 |
| Country: | México |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Caso clínico |
| English abstract | 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 |
| Disciplines: | Medicina |
| Keyword: | Gastroenterología, Terapéutica y rehabilitación, Genética, Colestasis, Fibrosis, Acido ursodeoxicólico, MDR3 |
| Keyword: | Medicine, Gastroenterology, Therapeutics and rehabilitation, Genetics, Cholestasis, Inflammation, Liver, Ursodeoxycholic acid, MDR3 |
| Full text: | Texto completo (Ver PDF) |
