Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure.
Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure.
复制标题
全身胆汁酸稳态的改变会导致肠衰竭儿科患者的肝脏疾病。
DOI：
10.1038/srep39264
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发表时间：
2016-12-15
影响因子：
4.6
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Xiao YT;Cao Y;Zhou KJ;Lu LN;Cai W
肠衰竭(IF)相关性肝病(IFALD)作为一种主要的并发症，在儿童IF患者中具有显著的发病率。然而，IFALD的发病机制仍不确定。我们在此探讨胆汁酸(BA)代谢异常在IFALD发病机制不明中的作用。结果发现，小儿IF患者的组织学表现为肝损伤，表现为肝胆管增生、炎性细胞浸润、肝细胞凋亡和不同阶段的纤维化。儿童IF患者血清和肝脏中BA成分发生改变，主要表现为以BA为主的成分。IF患者血清FGF19水平显著降低，且与回肠炎症分级呈负相关(r = −0.5 0，p <； 0.0 5)。在回肠，炎症分级与法尼醇X受体表达呈负相关(r = −0.5 5，p <； 0.0 5)。在肝脏中，诱导胆盐合成限速酶细胞色素P450 7A1的表达明显增加。综上所述，回肠炎症降低了FXR的表达，相应地降低了血清FGF19浓度，同时增加了肝脏胆汁酸的合成，从而导致IF患者的肝脏损害。
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.
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影响因子：
25.7
作者：
Pereira-Fantini, Prue M.;Lapthorne, Susan;Bines, Julie E.
通讯作者：
Bines, Julie E.
影响因子：
29.4
作者：
Modica, Salvatore;Petruzzelli, Michele;Moschetta, Antonio
通讯作者：
Moschetta, Antonio
影响因子：
4.9
作者：
Lenicek, Martin;Duricova, Dana;Vitek, Libor
通讯作者：
Vitek, Libor
影响因子：
13.5
作者：
Bedossa, P;Poynard, T
通讯作者：
Poynard, T
DOI：
10.1097/mpg.0b013e31817af979
发表时间：
2008-10-01
影响因子：
2.9
作者：
Diamanti, Antonella;Basso, Maria Sole;Gambarara, Manuela
通讯作者：
Gambarara, Manuela