Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure.
Sci Rep
; 6: 39264, 2016 12 15.
Article
en En
| MEDLINE
| ID: mdl-27976737
ABSTRACT
Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = -0.50, p < 0.05). In ileum, the inflammation grades were inversely associated with farnesoid X receptor (FXR) expression (r = -0.55, p < 0.05). In liver, the expression of induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácidos y Sales Biliares
/
Enfermedades Intestinales
/
Hepatopatías
Tipo de estudio:
Etiology_studies
Límite:
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Sci Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
China