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Regulation of bile acid metabolism in biliary atresia: reduction of FGF19 by Kasai portoenterostomy and possible relation to early outcome.
Journal of Internal Medicine ( IF 9.0 ) Pub Date : 2020-02-11 , DOI: 10.1111/joim.13028
H Johansson 1, 2 , J F Svensson 3, 4 , M Almström 3, 4 , N Van Hul 5 , M Rudling 6 , B Angelin 6 , G Nowak 1, 2 , B Fischler 7, 8 , E Ellis 1, 2
Affiliation  

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.

中文翻译:

胆道闭锁中胆汁酸代谢的调节:Kasai肠肠造口术可降低FGF19,并可能与早期结果有关。

背景技术成纤维细胞生长因子19(FGF19)在小肠中产生,并参与肝胆汁酸(BA)合成的抑制。在患有胆汁淤积性肝病的成人中,FGF19也在肝脏中表达,血清水平升高。这可能反映了一种缓解机制,可减轻肝内BAs升高引起的肝损伤。目的在非胆汁淤积型婴儿中,在胆道闭锁的早期和Kasai腔肠造口术(KPE)术后的短期随访中检查循环中的FGF19。还评估了FGF19,BA和BA合成标记与BA代谢相关因子肝基因表达之间的关系。方法从15名KPE患者中获取肝组织,门静脉和外周血样本。手术后4-6个月再采血。包括两个对照组。检查与手术有关的可能变化,并比较非胆汁淤积婴儿的胆道闭锁中的FGF19。结果胆道闭锁患者中KPE时,循环中的FGF19水平与其肝脏基因表达相关,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,且下降与胆红素和共轭鹅脱氧胆酸减少以及BA合成标志物C4升高有关。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的变化可能反映了肠肝循环的恢复水平,因此有必要对FGF19在胆汁淤积性肝中的作用进行进一步的长期研究。检查与手术有关的可能变化,并比较非胆汁淤积婴儿的胆道闭锁中的FGF19。结果胆道闭锁患者中KPE时,循环中的FGF19水平与其肝脏基因表达相关,并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,且下降与胆红素和共轭鹅脱氧胆酸减少以及BA合成标志物C4升高有关。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的变化可能反映了肠肝循环的恢复水平,因此有必要对FGF19在胆汁淤积性肝中的作用进行进一步的长期研究。检查与手术有关的可能变化,并比较非胆汁淤积婴儿的胆道闭锁中的FGF19。结果胆道闭锁患者中KPE时,循环中的FGF19水平与其肝脏基因表达相关,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,且下降与胆红素和共轭鹅脱氧胆酸减少以及BA合成标志物C4升高有关。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的变化可能反映了肝肠循环的恢复水平,因此有必要对FGF19在胆汁淤积性肝中的作用进行进一步的长期研究。结果胆道闭锁患者中KPE时,循环中的FGF19水平与其肝脏基因表达相关,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,且下降与胆红素和共轭鹅脱氧胆酸减少以及BA合成标志物C4升高有关。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的变化可能反映了肝肠循环的恢复水平,因此有必要对FGF19在胆汁淤积性肝中的作用进行进一步的长期研究。结果胆道闭锁患者中KPE时,循环中的FGF19水平与其肝脏基因表达相关,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,且下降与胆红素和共轭鹅脱氧胆酸减少以及BA合成标志物C4升高有关。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的变化可能反映了肝肠循环的恢复水平,因此有必要对FGF19在胆汁淤积性肝中的作用进行进一步的长期研究。FGF19水平显着降低,并且该下降与胆红素和缀合的鹅去氧胆酸的降低以及BA合成标记物C4的水平升高同时发生。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的变化可能反映了肠肝循环的恢复水平,因此有必要对FGF19在胆汁淤积性肝中的作用进行进一步的长期研究。FGF19水平显着降低,并且该下降与胆红素和缀合的鹅去氧胆酸的降低以及BA合成标记物C4的水平升高同时发生。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的变化可能反映了肝肠循环的恢复水平,因此有必要对FGF19在胆汁淤积性肝中的作用进行进一步的长期研究。
更新日期:2020-02-11
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