J Hepatol:奥贝胆酸促进原发性胆汁性肝硬化患者的肝胆汁酸排泄

2020-08-12 陶禹,华瑞 临床肝胆病杂志

奥贝胆酸(OCA)是核胆汁酸受体FXR的激动剂,调节肝胆汁酸代谢。本研究对熊去氧胆酸(UDCA)治疗反应不佳的原发性胆汁性肝硬化患者(PBC)进行了测试,已明确OCA治疗是否会影响结合胆汁酸的肝转运。

奥贝胆酸(OCA)是核胆汁酸受体FXR的激动剂,调节肝胆汁酸代谢。本研究对熊去氧胆酸(UDCA)治疗反应不佳的原发性胆汁性肝硬化患者(PBC)进行了测试,已明确OCA治疗是否会影响结合胆汁酸的肝转运。

来自奥胡斯大学医院消化内科的Kristoffer Kjærgaard等对8例碱性磷酸酶≥1.5 ULN且经UDCA治疗的PBC患者参与了这项随机双盲对照研究。在UDCA治疗的同时,患者被随机分配到两个组(安慰剂组,合并OCA治疗组),实验为3个月治疗期,并以1个月的洗脱期为间隔,不进行研究性治疗。在两个治疗周期后,我们计算胆汁酸在血液,肝细胞,胆小管和胆管常数的运输速率,并结合PET,利用胆汁酸追踪剂[N-methyl-11C] cholylsarcosine (11C-CSar),对肝脏进行扫描,并使用吲哚菁绿肝血液灌注。

DOI:https://doi.org/10.1016/j.jhep.2020.07.028

结果表明,与安慰剂相比,OCA使肝脏血液灌流增加了11%(p=0.045),使11C-CSar从血液进入肝细胞的单向摄取清除率增加了11%(p=0.01),并且11C-CSar从肝细胞进入胆管分泌的速率常数达到73%(p=0.03)。这导致OCA诱导的11C-Csar在肝细胞停留时间从组中位数11分钟减少到8分钟,相当于减少了30%(p=0.01)。

 

 

对UDCA治疗的PBC患者的研究表明,与安慰剂相比,OCA增加了结合胆汁酸示踪剂11C-CSar的转运,从而增加了内源性结合胆汁酸从肝细胞向胆小管的转运。因此,OCA减少了肝细胞暴露于潜在细胞毒性胆汁酸的时间。

原始出处:Kristoffer Kjærgaard , Kim Frisch , Michael Sørensen, et al. Obeticholic acid improves hepatic bile acid excretion in patients with primary biliary cholangitis. Journal of Hepatology. 2020.July 25.

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    2021-03-04 维他命
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    2020-08-27 14818eb4m67暂无昵称

    学习了

    0

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    2020-08-14 gwc384
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    2020-08-12 guging

    谢谢!最新的信息读起来就是收获大

    0

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