Table of Contents
Part I: Introduction
1. Overview of Mechanisms of Drug-Induced Liver Injury (DILI) and Key Challenges in DILI Research
Nabil Noureddin and Neil Kaplowitz
Part II: In Silico and Modeling Approaches
2. Detection, Elimination, Mitigation, and Prediction of Drug-Induced Liver Injury in Drug Discovery
Francois Pognan
3. Drug-Induced Liver Injury (DILI) Classification and Its Application on Human DILI Risk Prediction
Shraddha Thakkar, Minjun Chen, Huixiao Hong, Zhichao Liu, Hong Fang, and Weida Tong
4. Physicochemical Properties and Structural Alerts
Lilia Fisk, Nigel Greene, and Russ Naven
5. Quantitative Structure-Activity Relationship Models for Predicting Risk of Drug-Induced Liver Injury in Humans
Huixiao Hong, Jieqiang Zhu, Minjun Chen, Ping Gong, Chaoyang Zhang, and Weida Tong
6. An Introduction to DILIsym® Software, a Mechanistic Mathematical Representation of Drug-Induced Liver Injury
Christina Battista, Brett A. Howell, Scott Q. Siler, and Paul B. Watkins
Part III: In Vitro Technologies
7. Prediction of Human Liver Toxicity Using In Vitro Assays: Limitations and Opportunities
Franck A. Atienzar and Jean-Marie Nicolas
8. Use of Liver-Derived Cell Lines for the Study of Drug-Induced Liver Injury
Zhen Ren, Si Chen, Baitang Ning, and Lei Guo
9. Evaluation of Drug-induced Liver Injuries (DILI) with Human Hepatocytes: Scientific Rationale and Experimental Approaches
Albert P. Li
10. Status and Use of Induced Pluripotent Stem Cells (iPSCs) in Toxicity Testing
Min Wei Wong, Chris S. Pridgeon, Constanze Schlott, B. Kevin Park, and Christopher E.P. Goldring
11. Engineered Human Liver Co-Cultures for Investigating Drug-Induced Liver Injury
Chase P. Monckton, and Salman R. Khetani
12. Status and Future of 3D Cell Culture in Toxicity Testing
Monicah A. Otieno, Jinping Gan, and William Proctor
13. Reactive Metabolite Assessment in Drug Discovery and Development in Support of Safe Drug Design
Axel Pähler
14. In Vitro Assessment of Mitochondrial Toxicity to Predict Drug-Induced Liver Injury
Mathieu Porceddu, Nelly Buron, Pierre Rustin, Bernard Fromenty, and Annie Borgne-Sanchez
15. Bile Salt Export Pump: Drug-Induced Liver Injury and Assessment Approaches
Ruitang Deng
16. High Content Screening for Prediction of Human Drug-Induced Liver Injury
Mikael Persson
17. Interpretation, Integration, and Implementation of In Vitro Assay Data: The Predictive Toxicity Challenge
Deborah S. Light, Michael D. Aleo, and J. Gerry Kenna
Part IV: Methodologies Applied in Regulatory Science
18. Perspectives on the Regulatory and Clinical Science of Drug-Induced Liver Injury (DILI)
Mark I. Avigan and Monica A. Muñoz
19. Regulatory Toxicological Studies: Identifying Drug-Induced Liver Injury Using Nonclinical Studies
Elizabeth Hausner and Imran Khan
20. Hy’s Law and eDISH for Clinical Studies
John Senior and Ted Guo
21. Variability in Baseline Liver Test Values in Clinical Trials: Challenges in Enhancing Drug-Induced Liver Injury Assessment in Subjects with Liver Disease
Bereket Tesfaldet, Gyorgy Csako, Tejas Patel, Md Shamsuzzaman, and Eileen Navarro Almario
22. Postmarketing Surveillance of Drug-Induced Liver Injury
S. Christopher Jones, Cindy Kortepeter, and Allen D. Brinker
Part V: Methodologies for Clinical Studies
23. Host Risk Modifiers in Idiosyncratic Drug-Induced Liver Injury (DILI) and Its Interplay with Drug Properties
Camilla Stephens, M. Isabel Lucena, and Raúl J. Andrade
24. Human Leukocyte Antigen (HLA) and Other Genetic Risk Factors in Drug-Induced Liver Injury (DILI)
Ann K. Daly
25. Immune Mechanisms in Drug-Induced Liver Injury
Hartmut Jaeschke and Dean J. Naisbitt
26. Translational and Mechanistic Biomarkers of Drug-Induced Liver Injury
Daniel J. Antoine
27. Causality Assessment Methods in Drug-Induced Liver Injury
Rolf Teschke and Gaby Danan
Part VI: New Emerging Technologies
28. Circulating MicroRNAs as Novel Biomarkers of Drug-Induced Liver Injury in Humans
Julian Krauskopf, Jos C. Kleinjans, and Theo M. de Kok
29. Systems Microscopy Approaches in Unraveling and Predicting Drug-Induced Liver Injury (DILI)
Marije Niemeijer, Steven Hiemstra, Steven Wink, Wouter den Hollander, Bas ter Braak, and Bob van de Water
30. Non-Invasive Pre-Clinical and Clinical Imaging of Liver Transporter Function Relevant to Drug-Induced Liver Injury
J. Gerry Kenna, John C. Waterton, Andreas Baudy, Aleksandra Galetin, Catherine D.G. Hines, Paul Hockings, Manishkumar Patel, Daniel Scotcher, Steven Sourbron, Sabina Ziemian, and Gunnar Schuetz