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Clin Gastroenterol Hepatol: 血清牛磺胆酸水平高与药物引起的肝损伤的严重程度相关

2021-04-25 MedSci原创 MedSci原创

药物性肝损伤(DILI)是临床上最常见的肝损伤原因之一,DILI可以具有不同的临床特征和参差不齐的预后结果,患者一旦出现黄疸则会导致很高的死亡率。

      药物性肝损伤(DILI)是临床上最常见的肝损伤原因之一,DILI可以具有不同的临床特征和参差不齐的预后结果,患者一旦出现黄疸则会导致很高的死亡率。在临床工作中迫切需要一些非侵入性血清生物标志物来判断肝损伤的严重程度。最近有证据表明胆汁酸(BA)失调在DILI中起着关键作用,因为胆汁排泄是消除胆红素的主要途径。因此,本项研究旨在评估血清胆汁酸水平与DILI的严重程度和预后之间的关联,

 

      研究人员收集了2018年8月至2019年8月间共95例DILI患者(中位年龄为53岁;女性为73.7%)进行了这项前瞻性研究。对患者的年龄,性别和体重指数进行了健康对照组匹配(n = 100;健康对照组)和慢性乙型肝炎患者对照(n = 105; CHB对照)。在基线以及DILI发作后1周,1个月,3个月和6个月以及肝脏生化指标恢复,肝衰竭或肝移植时收集了各项临床资料。使用高效液相色谱质谱法测量血清胆汁酸水平,并通过免疫组织化学分析了肝活检标本中特异性蛋白的表达。

 

      研究结果显示在DILI患者和健康对照之间,分析的37种胆汁酸中有30种的水平存在显着差异。牛磺胆酸(TCA),糖胆酸,牛磺去氧胆酸和糖醛去氧胆酸水平的变化与胆红素水平升高和DILI的严重程度相关,也与CHB有关。Cox回归分析表明,仅TCA水平的变化与DILI的生化指标独立相关。TCA水平(≥1955.41 nmol / L),患者年龄和DILI严重程度与DILI发作后6个月的血液生化异常相关(AUC: 0.81; 95%CI: 0.71-0.88;敏感性0.69;特异性为0.81)。然而,肝活检中胆小管中特异性蛋白(BSEP)含量较低与血清胆汁酸水平改变有关。

图:牛磺胆酸水平与肝损伤的关系

      在这项前瞻性研究中,研究人员发现TCA的血清水平与DILI的严重程度和临床预后有关。肝脏组织中特异性蛋白(BSEP)的蛋白表达降低与血清胆汁酸水平的改变有关。

 

 

原始出处:

Qiuju Tian. Et al. A High Serum Level of Taurocholic Acid Is Correlated With the Severity and Resolution of Drug-induced Liver Injury. Clin Gastroenterol Hepatol.2021.

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    2021-04-27 gwc384
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    2021-04-25 jyzxjiangqin

    好文章!

    0

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2019年3月,欧洲肝脏研究学会(EASL)发布了药物性肝损伤指南,特异性药物肝损伤是肝病科医生面临的最具挑战的肝病之一,由于临床实践中药物种类繁多,药物性肝损伤具有多种临床和病理表型,且缺乏特定的生物标志物。本文主要总结了当前关于药物性肝损伤的危险因素、诊断、管理以及最小化风险策略的相关内容并提出指导建议。

研究人员发现治疗药物性肝损伤的新靶标:血小板反应蛋白-1

2019年实验生物学(EB)会议上报道的临床前研究结果表明,增加血小板反应蛋白-1的水平可以减轻过量对乙酰氨基酚诱导的肝损伤。

Hepatology:诊断药物性肝损伤与预后判断的候选生物标志物

在鉴别DILI患者时,GLDH似乎比miR-122更有用。K18、OPN和MCSFR等在急性DILI事件中预后价值较大。在大型前瞻性研究中对这些生物标记物的连续评估将有助于进一步描述它们在DILI诊断和管理中的作用。

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