Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.
Daniel J. Antoine,James W. Dear,Philip J. Starkey Lewis,Vivien Platt,Judy Coyle,Moyra Masson,Ruben Thanacoody,Alasdair Gray,David J. Webb,Jonathan G. Moggs,D. Nicholas Bateman,Christopher E. Goldring,B. Kevin Park +12 more
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TLDR
Elevations in plasma miR‐122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range.About:
This article is published in Hepatology.The article was published on 2013-08-01 and is currently open access. It has received 374 citations till now. The article focuses on the topics: acetaminophen overdose & Alanine transaminase.read more
Citations
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The transformation in biomarker detection and management of drug-induced liver injury.
Rachel J. Church,Paul B. Watkins +1 more
TL;DR: It is believed that utilization of a panel of traditional and newer biomarkers in conjunction with quantitative systems pharmacology modelling approaches will transform DILI detection and risk management.
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Translational biomarkers of acetaminophen-induced acute liver injury
Richard D. Beger,Sudeepa Bhattacharyya,Sudeepa Bhattacharyya,Xi Yang,Pritmohinder S. Gill,Pritmohinder S. Gill,Laura K. Schnackenberg,Jinchun Sun,Laura P. James,Laura P. James +9 more
TL;DR: The following review provides a summary of the systems biology discovery process, analytical validation of biomarkers and translation of omics biomarkers from the nonclinical to clinical setting in APAP-induced liver injury.
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The diagnosis and management of idiosyncratic drug‐induced liver injury
Ammar Hassan,Robert J. Fontana +1 more
TL;DR: A number of promising diagnostic, prognostic and mechanistic serum and genetic biomarkers may help improve the understanding of the pathogenesis and treatment of idiosyncratic DILI.
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Plasma paracetamol concentration at hospital presentation has a dose-dependent relationship with liver injury despite prompt treatment with intravenous acetylcysteine
David G Cairney,Hannah Beckwith,Khalid Al-Hourani,Michael Eddleston,D. Nicholas Bateman,James W. Dear +5 more
TL;DR: Patients with increased concentrations of plasma paracetamol at hospital presentation are at higher risk of liver injury even when intravenous NAC is promptly administered before there is biochemical evidence of toxicity, which supports theoretical concerns that the current intravenous dose of NAC may be too low in the setting of higher par acetamol exposure.
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Massive paracetamol overdose: an observational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM-2)
Angela L. Chiew,Geoffrey K. Isbister,Katharine A. Kirby,Colin B. Page,Betty S. Chan,Nicholas A. Buckley +5 more
TL;DR: Massive paracetamol overdose can result in hepatotoxicity despite early treatment, and treatment with increased acetylcysteine dose within 21 h was associated with a significant reduction in hepatOToxicity.
References
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Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
Tiziana Bonaldi,Fabio Talamo,Paola Scaffidi,Denise Ferrera,Annalisa Porto,Angela Bachi,Anna Rubartelli,Alessandra Agresti,Marco Bianchi +8 more
TL;DR: It is shown here that in all cells HMGB1 shuttles actively between the nucleus and cytoplasm, and secreted when monocytic cells receive an appropriate second signal.
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Circulating microRNAs, potential biomarkers for drug-induced liver injury
Kai Wang,Shile Zhang,Bruz Marzolf,Pamela Troisch,Amy Brightman,Zhiyuan Hu,Leroy Hood,David J. Galas +7 more
TL;DR: It is demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose- and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier.
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Characterization of microRNA expression profiles in normal human tissues
TL;DR: A global view of tissue distribution of miRNAs in relation to their chromosomal locations and genomic structures is presented to support their tissue-specific functional roles to regulate the physiologies of the normal tissues in which they are expressed.
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Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity
TL;DR: The formation of oxidants and the defense mechanisms available for cells are addressed and knowledge is applied to better understand mechanisms of drug hepatotoxicity, especially acetaminophen-induced liver injury.
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The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation.
Mitchell R. McGill,Matthew R. Sharpe,C. David Williams,Mohammad Taha,Steven C. Curry,Hartmut Jaeschke +5 more
TL;DR: It is suggested that mitochondrial damage and nuclear DNA fragmentation are likely to be critical events in APAP hepatotoxicity in humans, resulting in necrotic cell death.