Regulation of bile acid metabolism in biliary atresia: reduction of FGF19 by Kasai portoenterostomy and possible relation to early outcome
Regulation of bile acid metabolism in biliary atresia: reduction of FGF19 by Kasai portoenterostomy and possible relation to early outcome
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DOI：
10.1111/joim.13028
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发表时间：
2020-02-11
影响因子：
11.1
通讯作者：
Ellis, E.
中科院分区：
文献类型：
--
作者：
Johansson, H.;Svensson, J. F.;Ellis, E.
背景 成纤维细胞生长因子 19 (FGF19) 在小肠中产生，参与抑制肝胆汁酸 (BA) 合成。 FGF19 也在肝脏中表达，患有胆汁淤积性肝病的成人的血清水平升高。这可能反映了抑制肝内 BA 增加引起的肝损伤的救援机制。 目的 检测与非胆汁淤积婴儿相关的胆道闭锁早期阶段和 Kasai 门肠造口术 (KPE) 后短期随访时的循环 FGF19。还评估了FGF19、BAs和BA合成标志物以及参与BA代谢的因子的肝脏基因表达之间的关系。方法采集KPE的15名患者的肝组织、门静脉和外周血样本；手术后4-6个月收集额外的血液。包括两个对照组；检查与手术相关的可能变化，并比较胆道闭锁与非胆汁淤积婴儿的 FGF19。结果 胆道闭锁 KPE 时循环 FGF19 水平与其肝脏基因表达相关，且与非胆汁淤积婴儿相比，其水平升高。随访时，FGF19 水平显着降低，这种下降与胆红素和结合鹅去氧胆酸的降低以及 BA 合成标记物 C4 水平的升高同时发生。 结论 胆道闭锁中循环 FGF19 升高是肝源性的，在 KPE 后降低。血清FGF19的变化可能反映肠肝循环的恢复水平，这值得进一步长期研究FGF19在胆汁淤积性肝脏中的作用。
Background Fibroblast growth factor 19 (FGF19) is produced in the small intestine and is involved in suppression of hepatic bile acid (BA) synthesis. FGF19 is also expressed in the liver and serum levels are elevated in adults with cholestatic liver disease. This may reflect a rescue mechanism to dampen liver injury caused by increased intrahepatic BAs.Objectives To examine circulating FGF19 at early stages of biliary atresia and at short-term follow-up post-Kasai portoenterostomy (KPE) in relation to noncholestatic infants. The relationship between FGF19, BAs and markers for BA synthesis and hepatic gene expression of factors involved in BA metabolism were also evaluated.Methods Liver tissue, portal and peripheral blood samples were obtained from fifteen patients at KPE; additional blood was collected 4-6 months after surgery. Two control groups were included; to examine possible changes related to surgery and to compare FGF19 in biliary atresia to noncholestatic infants.Results Circulating FGF19 levels correlated to its hepatic gene expression at time of KPE in biliary atresia and levels were elevated compared to noncholestatic infants. At follow-up, FGF19 levels were markedly reduced, and the decline coincided with reductions in bilirubin and conjugated chenodeoxycholic acid and with increased levels of the BA synthesis marker C4.Conclusion Elevated circulating FGF19 in biliary atresia is of hepatic origin and reduced following KPE. Changes in serum FGF19 may reflect the level of restoration of the enterohepatic circulation, and this warrants further long-term studies on the role of FGF19 in the cholestatic liver.