Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.
Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.
复制标题
DOI：
10.1002/hep.29802
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Watkins PB
中科院分区：
文献类型：
--
作者：
Church RJ;Kullak-Ublick GA;Aubrecht J;Bonkovsky HL;Chalasani N;Fontana RJ;Goepfert JC;Hackman F;King NMP;Kirby S;Kirby P;Marcinak J;Ormarsdottir S;Schomaker SJ;Schuppe-Koistinen I;Wolenski F;Arber N;Merz M;Sauer JM;Andrade RJ;van Bömmel F;Poynard T;Watkins PB
目前的血液生物标志物在检测药物性肝损伤（DILI）和预测其预后方面并不理想。我们试图描述14种有前途的DILI生物标志物候选物的自然变异性和性能特征。对健康志愿者（n=192和81）、安全服用潜在肝毒性药物且无不良反应的受试者（n=55和92）和DILI患者（n=98、28和143）的血清或血浆进行了microRNA-122 （miR-122）、谷氨酸脱氢酶（GLDH）、总角蛋白18 （K18）、caspase cleaved K18 （ccK18）、谷胱甘肽s -转移酶α (GSTα)、甲胎蛋白（AFP）、精氨酸酶-1 （ARG1）、骨桥蛋白（OPN）、山梨糖醇脱氢酶（SDH）、脂肪酸结合蛋白（FABP1）、钙粘蛋白-5 （CDH5）、巨噬细胞集落刺激因子受体（MCSFR）、对氧磷酶1 （PON1，正常化为凝血酶原蛋白）和白细胞来源的趋化素-2 （LECT2）。与健康志愿者相比，DILI患者中大多数候选生物标志物显著改变。GLDH与金标准丙氨酸转氨酶（ALT）的相关性比miR-122更密切，健康志愿者中miR-122水平的个体间和个体内差异令人惊讶。血清K18、OPN和MCSFR水平与dili发病6个月内肝脏相关死亡或移植最密切相关。结合K18和MCSFR水平，使用终末期肝病模型（MELD）预测DILI患者的预后得到改善。结论：GLDH在识别DILI患者方面似乎比miR-122更有用。K18、OPN和MCSFR是预测急性DILI事件预后的有希望的候选指标。在大型前瞻性研究中对这些生物标志物进行系列评估将有助于进一步描述它们在DILI诊断和管理中的作用。
Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of fourteen promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n=192 and =81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n=55 and =92) and DILI patients (n=98, =28, and =143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total keratin 18 (K18), caspase cleaved K18 (ccK18), glutathione S-transferase alpha (GSTα), alpha fetoprotein (AFP), arginase-1 (ARG1), osteopontin (OPN), sorbitol dehydrogenase (SDH), fatty acid binding protein (FABP1), cadherin-5 (CDH5), macrophage colony stimulating factor receptor (MCSFR), paraoxonase 1 (PON1, normalized to prothrombin protein), and leucocyte cell-derived chemotaxin-2 (LECT2). Most candidate biomarkers were significantly altered in DILI cases compared to healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase (ALT) than miR-122 and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among the healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplant within 6 months of DILI-onset. Prediction of prognosis among DILI patients using Model for End-stage Liver Disease (MELD) was improved by incorporation of K18 and MCSFR levels. Conclusion: GLDH appears to be more useful than miR-122 in identifying DILI patients. K18, OPN and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management.
登录
查看更多内容
影响因子：
13.5
作者：
Antoine, Daniel J.;Dear, James W.;Lewis, Philip Starkey;Platt, Vivien;Coyle, Judy;Masson, Moyra;Thanacoody, Ruben H.;Gray, Alasdair J.;Webb, David J.;Moggs, Jonathan G.;Bateman, D. Nicholas;Goldring, Christopher E.;Park, B. Kevin
通讯作者：
Park, B. Kevin
影响因子：
3.4
作者：
Purkins, L;Love, ER;Rapeport, WG
通讯作者：
Rapeport, WG
影响因子：
25.7
作者：
Antoine, Daniel J.;Jenkins, Rosalind E.;Dear, James W.;Williams, Dominic P.;McGill, Mitchell R.;Sharpe, Matthew R.;Craig, Darren G.;Simpson, Kenneth J.;Jaeschke, Hartmut;Park, B. Kevin
通讯作者：
Park, B. Kevin
DOI：
10.1016/j.bbrc.2004.03.057
发表时间：
2004-04-30
影响因子：
3.1
作者：
Arai, M;Yokosuka, O;Seki, N
通讯作者：
Seki, N
对乙酰氨基酚过量且预后不良的患者的血清线粒体生物标志物和损伤相关分子模式较高。
影响因子：
13.5
作者：
McGill, Mitchell R.;Staggs, Vincent S.;Sharpe, Matthew R.;Lee, William M.;Jaeschke, Hartmut
通讯作者：
Jaeschke, Hartmut