Hepatology:诊断药物性肝损伤与预后判断的候选生物标志物

2018-01-28 MedSci MedSci原创

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。

目前血清生物标志物在检测药物性肝损伤(DILI)和判断疾病预中的表现并不是最佳的。本研究的目的是验证14个有潜在诊断DILI价值的生物标志物的效能。

取多组健康志愿者(n=192, =81),服用潜在肝毒性药物无不良反应的患者(n=55, =92)和DILI患者(n=98, =28, =143)的血清或血浆。检测这些血清或血浆的微microRNA-122(miR-122)、谷氨酸脱氢酶(GLDH), 角蛋白18(K18), 半胱天冬酶裂解片段K18(ccK18), 谷胱甘肽S转移酶a(GSTalpha),α胎蛋白(法新社), arginase-1, 骨桥蛋白(OPN), 山梨糖醇脱氢酶(SDH), 脂肪酸结合蛋白(FABP1), cadherin-5(CDH5)、巨噬细胞集落刺激因子受体(MCSFR), paraoxonase 1(PON1),和白细胞细胞衍生趋化因子2 (LECT2)等含量。

相比健康对照者,DILI患者血清中的大多数候选血清生物学标致物的含量发生改变。与miR-122相比,谷氨酸脱氢酶(GLDH)与金标准丙氨酸转氨酶(ALT)相关性更强。在健康的志愿者中,miR-122水平的内部和个体间的可变性较大。血清K18、OPN和MCSFR水平在DILI发病后6个月内与肝病相关死亡或移植的相关性最强。K18和MCSFR等血清学指标与终末期肝病模型(MELD)的结合提高了DILI患者疾病预后的判断。

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诊断管理中的作用。

原始出处

Church RJ, Kullak-Ublick GA, Aubrecht J, et al. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort. Hepatology, 2018 Jan 22. doi: 10.1002/hep.29802.

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    2018-01-30 gwc384
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