Biomarkers of drug-induced liver injury: a mechanistic perspective through acetaminophen hepatotoxicity.
Biomarkers of drug-induced liver injury: a mechanistic perspective through acetaminophen hepatotoxicity.
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DOI：
10.1080/17474124.2021.1857238
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发表时间：
2021-04
影响因子：
3.9
通讯作者：
Jaeschke H
中科院分区：
文献类型：
--
作者：
Umbaugh DS;Jaeschke H
药物性肝损伤是一个严重的临床问题。许多用于识别和预测药物性肝损伤（DILI）的循环生物标志物已经被提出。生物标志物主要基于对潜在DILI的机制理解，通常在对乙酰氨基酚过量的情况下。新的生物标志物组已经出现，与DILI后的恢复/再生有关，而不是与损伤有关。我们探讨这些新的生物标志物的临床相关性和局限性，包括最近的争议。细胞外囊泡也成为一种很有前途的生物标志物载体，尽管ev的生物学作用可能会限制其临床用途。生物标志物发现的新技术途径也进行了探索。最近的临床研究已经证实了一些新的生物标志物，如细胞角蛋白-18、巨噬细胞集落刺激因子受体和骨桥蛋白对DILI预后的疗效。DILI的低患病率是DILI生物标志物开发的固有限制。进一步了解DILI的机制和利用技术进步（如机器学习和组学方法）是改进最新一代生物标志物的必要条件。组学方法与机器学习的结合为癌症研究带来了新的见解，DILI研究准备利用这些技术发现和开发生物标志物。
Liver injury induced by drugs is a serious clinical problem. Many circulating biomarkers for identifying and predicting drug-induced liver injury (DILI) have been proposed. Biomarkers are mainly predicated on the mechanistic understanding of the underlying DILI, often in the context of acetaminophen overdose. New panels of biomarkers have emerged that are related to recovery/regeneration rather than injury following DILI. We explore the clinical relevance and limitations of these new biomarkers including recent controversies. Extracellular vesicles have also emerged as a promising vector of biomarkers, although the biological role for EVs may limit their clinical usefulness. New technological approaches for biomarker discovery are also explored. Recent clinical studies have validated the efficacy of some of these new biomarkers, cytokeratin-18, macrophage colony stimulating factor receptor, and osteopontin for DILI prognosis. Low prevalence of DILI is an inherent limitation to DILI biomarker development. Furthering mechanistic understanding of DILI and leveraging technological advances (e.g. machine learning and omics approaches) is necessary to improve upon the newest generation of biomarkers. The integration of omics approaches with machine learning has led to novel insights in cancer research and DILI research is poised to leverage these technologies for biomarker discovery and development.
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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：
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：
10.1002/hep.29802
发表时间：
2019-03
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
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
通讯作者：
Watkins PB
影响因子：
6.7
作者：
Craig, Darren G. N.;Lee, Patricia;Simpson, Kenneth J.
通讯作者：
Simpson, Kenneth J.
影响因子：
6.1
作者：
Albrecht, Wiebke;Kappenberg, Franziska;Hengstler, Jan G.
通讯作者：
Hengstler, Jan G.