Main description:

This book provides a comprehensive view of the methodologies used for the study of liver toxicity encountered throughout the whole life cycle of a drug, from drug discovery, to clinical trial, post-marketing, and even clinical practice. Organized into six sections, the first section introduces the mechanisms contributing to drug-induced liver toxicity. The second and third section explore in silico and in vitro approaches used to help mitigate hepatotoxicity liability at the early stages of drug development. The fourth section describes methodologies applied in regulatory processes, including preclinical studies, clinical trials, and post-marketing surveillance. The fifth section discusses clinical hepatotoxicity. Emerging technologies are examined in the final section. As a volume in the Methods in Pharmacology and Toxicology series, chapters include the kind of expert advice that will lead to optimal results.
Authoritative and practical, Drug-Induced Liver Toxicity serves all those who aim to improve assessment and understanding of hepatotoxic potentials of new medications and marketed drugs.

Chapter 30 is open access under a CC BY 4.0 license via link.springer.com.

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 (R) 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 Pahler

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. Munoz

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 Raul 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