Journal ArticleDOI
Idiosyncratic drug-induced liver injury: an update on the 2007 overview.
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TLDR
An update on the epidemiology, pathogenic mechanisms, diagnosis, outcome, risk factors for idiosyncratic drug-induced hepatotoxicity, specific classes of drug hepatot toxicity and biomarkers to predict DILI are covered.Abstract:
Introduction: Idiosyncratic drug induced liver injury (DILI) is rare, with an incidence of approximately 19 per 100,000 treated individuals. Areas covered: An update on the epidemiology, pathogenic mechanisms, diagnosis, outcome, risk factors for idiosyncratic drug-induced hepatotoxicity, specific classes of drug hepatotoxicity and biomarkers to predict DILI are covered. Cumulative drug exposure and HLA phenotypes play an important role in the pathogenesis of DILI. Patients who present with suspected DILI and jaundice should have biliary obstruction and acute viral hepatitis, including hepatitis E excluded. Immune-mediated DILI will respond to steroid therapy. Patients with an elevated bilirubin and a hepatocellular pattern of liver function tests have severe liver injury with a mortality of greater than 10% and a risk of acute liver failure. Women have an increased risk of hepatocellular DILI. Antibiotics, anticonvulsants, and antidepressant therapy remain the commonest causes of DILI in the Western Hemi...read more
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Journal ArticleDOI
The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature.
TL;DR: The findings of this review should alert the physician to carefully review the appropriateness of AD prescription on an individual basis and to consider alternative treatments if available.
Journal ArticleDOI
CSH guidelines for the diagnosis and treatment of drug-induced liver injury
Yue-cheng Yu,Yimin Mao,Chengwei Chen,Jinjun Chen,Jun Chen,Wen-Ming Cong,Yang Ding,Zhongping Duan,Qingchun Fu,Xiao-yan Guo,Peng Hu,Xi-qi Hu,Jidong Jia,Rongtao Lai,Dongliang Li,Yingxia Liu,Lungen Lu,Shi-wu Ma,Xiong Ma,Yuemin Nan,Hong Ren,Tao Shen,Hao Wang,J.Z. Wang,Tai-ling Wang,Xiaojin Wang,Lai Wei,Qing Xie,Wen Xie,Chang-qing Yang,Dongliang Yang,Yanyan Yu,Minde Zeng,Li Zhang,Xinyan Zhao,Hui Zhuang +35 more
TL;DR: The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.
Journal ArticleDOI
Toxicology Strategies for Drug Discovery: Present and Future.
Eric A.G. Blomme,Yvonne Will +1 more
TL;DR: An overview of toxicology approaches and models that can be used in pharmaceutical Discovery at the series/lead identification and lead optimization stages to guide and inform chemistry efforts, as well as a personal view on how to best use them to meet nonclinical safety-related attrition objectives consistent with a sustainable pharmaceutical R&D model are provided.
Journal ArticleDOI
The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death
Laleh Kamalian,Amy E. Chadwick,Mark Bayliss,Neil French,Mario Monshouwer,Jan Snoeys,B. Kevin Park +6 more
TL;DR: These studies demonstrate the utility of HepG2 cells for the identification of mitochondrial toxins which act directly on the electron transport chain and that the dual assessment of ATP content alongside cytotoxicity provides an enhanced mechanistic understanding of the causes of toxicity.
Journal ArticleDOI
A transcriptomics data-driven gene space accurately predicts liver cytopathology and drug-induced liver injury.
Pekka Kohonen,Juuso Parkkinen,Egon Willighagen,Egon Willighagen,Rebecca Ceder,Krister Wennerberg,Samuel Kaski,Roland C. Grafström +7 more
TL;DR: A ‘big data compacting and data fusion’—concept to capture diverse adverse outcomes on cellular and organismal levels is utilized to capture unanticipated harmful effects of chemicals and drug molecules.
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Journal ArticleDOI
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Journal ArticleDOI
Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries.
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