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Protocol
Quantitative Systems Toxicology and Drug Development: The DILIsym Experience
DILIsym® is a Quantitative Systems Toxicology (QST) model that has been developed over the last decade by a public-private partnership to predict the liver safety liability in new drug candidates. DILIsym integra...
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Article
HLA associations with infliximab-induced liver injury
Biomarkers that are able to identify patients at risk of drug-induced liver injury (DILI) after treatment with infliximab could be important in increasing the safety of infliximab use. We performed a genetic a...
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Article
Polygenic architecture informs potential vulnerability to drug-induced liver injury
Drug-induced liver injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market; this is partially due to the inability to identify patients who are at risk1. ...
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Article
Drug-induced liver injury
Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when an individual is exposed to toxic doses of some compounds or as an unpredict...
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Article
Open AccessAnalyzing the Mechanisms Behind Macrolide Antibiotic-Induced Liver Injury Using Quantitative Systems Toxicology Modeling
Macrolide antibiotics are commonly prescribed treatments for drug-resistant bacterial infections; however, many macrolides have been shown to cause liver enzyme elevations and one macrolide, telithromycin, has...
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Article
Correction to: Liver Safety of Fasiglifam (TAK-875) in Patients with Type 2 Diabetes: Review of the Global Clinical Trial Experience
In the original publication of the article, the ALT and AST values in Fig. 5a–e were capped at 10× ULN, which did not accurately reflect the narrative provided for each case. In this correction, the original F...
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Article
Liver Safety of Fasiglifam (TAK-875) in Patients with Type 2 Diabetes: Review of the Global Clinical Trial Experience
Fasiglifam (TAK-875) is a G protein-coupled receptor 40 agonist that was being investigated for treatment of type 2 diabetes mellitus (T2DM). A development program was terminated late in phase III clinical tri...
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Protocol
An Introduction to DILIsym® Software, a Mechanistic Mathematical Representation of Drug-Induced Liver Injury
Drug-induced liver injury (DILI) is one of the primary reasons why a new drug candidate may fail during development. To address this challenge, a mathematical representation, DILIsym®, has been developed as a ...
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Article
Open AccessClinical Pattern of Tolvaptan-Associated Liver Injury in Subjects with Autosomal Dominant Polycystic Kidney Disease: Analysis of Clinical Trials Database
Subjects with autosomal dominant polycystic kidney disease (ADPKD) who were taking tolvaptan experienced aminotransferase elevations more frequently than those on placebo in the TEMPO 3:4 (Tolvaptan Efficacy a...
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Article
Open AccessLiver Safety Assessment in Special Populations (Hepatitis B, C, and Oncology Trials)
The FDA guidance for industry in the premarketing clinical evaluation of drug-induced liver injury (DILI) is the most specific regulatory guidance currently available and has been useful in setting standards f...
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Article
Open AccessThe Clinical Liver Safety Assessment Best Practices Workshop: Rationale, Goals, Accomplishments and the Future
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Article
Open AccessMethodology to Assess Clinical Liver Safety Data
Analysis of liver safety data has to be multivariate by nature and needs to take into account time dependency of observations. Current standard tools for liver safety assessment such as summary tables, individ...
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Article
Open AccessCausality Assessment for Suspected DILI During Clinical Phases of Drug Development
Causality assessment is a critical step in establishing the diagnosis of drug induced liver injury (DILI) during drug development. DILI may resemble almost any type of liver disease, and often presents a serio...
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Article
Open AccessLiver Safety Assessment: Required Data Elements and Best Practices for Data Collection and Standardization in Clinical Trials
A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and stan...
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Article
Open AccessBenign elevations in serum aminotransferases and biomarkers of hepatotoxicity in healthy volunteers treated with cholestyramine
There are currently no serum biomarkers capable of distinguishing elevations in serum alanine aminotransferase (ALT) that portend serious liver injury potential from benign elevations such as those occurring d...
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Article
Anti-Tuberculosis Drug-Induced Liver Injury in Shanghai: Validation of Hy’s Law
The most reliable liver safety signal in a clinical trial is considered to be ‘Hy’s Law cases’ defined as subjects experiencing hepatocellular injury and serum bilirubin elevations with no more likely cause th...
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Article
Open AccessSerum acute phase reactants hallmark healthy individuals at risk for acetaminophen-induced liver injury
Acetaminophen (APAP) is a commonly used analgesic. However, its use is associated with drug-induced liver injury (DILI). It is a prominent cause of acute liver failure, with APAP hepatotoxicity far exceeding o...
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Article
Current Challenges and Controversies in Drug-Induced Liver Injury
Current key challenges and controversies encountered in the identification of potentially hepatotoxic drugs and the assessment of drug-induced liver injury (DILI) are covered in this article.
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Article
Open AccessUnderstanding hepatotoxicity – from patients to mice to computer
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Article
In vitro to in vivo extrapolation and species response comparisons for drug-induced liver injury (DILI) using DILIsym™: a mechanistic, mathematical model of DILI
Drug-induced liver injury (DILI) is not only a major concern for all patients requiring drug therapy, but also for the pharmaceutical industry. Many new in vitro assays and pre-clinical animal models are being...
