Drug-Induced Liver Toxicity

1. Front Matter

   Pages i-xx

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2. Introduction

   1. Front Matter

      Pages 1-1

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   2. Overview of Mechanisms of Drug-Induced Liver Injury (DILI) and Key Challenges in DILI Research

      • Nabil Noureddin, Neil Kaplowitz

      Pages 3-18

3. In Silico and Modeling Approaches

   1. Front Matter

      Pages 19-19

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   2. Detection, Elimination, Mitigation, and Prediction of Drug-Induced Liver Injury in Drug Discovery

      • Francois Pognan

      Pages 21-43

   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, Weida Tong

      Pages 45-59

   4. Physicochemical Properties and Structural Alerts

      • Lilia Fisk, Nigel Greene, Russ Naven

      Pages 61-76

   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, Weida Tong

      Pages 77-100

   6. An Introduction to DILIsym® Software, a Mechanistic Mathematical Representation of Drug-Induced Liver Injury

      • Christina Battista, Brett A. Howell, Scott Q. Siler, Paul B. Watkins

      Pages 101-121

4. In Vitro Technologies

   1. Front Matter

      Pages 123-123

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   2. Prediction of Human Liver Toxicity Using In Vitro Assays: Limitations and Opportunities

      • Franck A. Atienzar, Jean-Marie Nicolas

      Pages 125-150

   3. Use of Liver-Derived Cell Lines for the Study of Drug-Induced Liver Injury

      • Zhen Ren, Si Chen, Baitang Ning, Lei Guo

      Pages 151-177

   4. Evaluation of Drug-Induced Liver Injuries (DILI) with Human Hepatocytes: Scientific Rationale and Experimental Approaches

      • Albert P. Li

      Pages 179-197

   5. Status and Use of Induced Pluripotent Stem Cells (iPSCs) in Toxicity Testing

      • Min Wei Wong, Chris S. Pridgeon, Constanze Schlott, B. Kevin Park, Christopher E. P. Goldring

      Pages 199-212

   6. Engineered Human Liver Cocultures for Investigating Drug-Induced Liver Injury

      • Chase P. Monckton, Salman R. Khetani

      Pages 213-248

   7. Status and Future of 3D Cell Culture in Toxicity Testing

      • Monicah A. Otieno, Jinping Gan, William Proctor

      Pages 249-261

   8. Reactive Metabolite Assessment in Drug Discovery and Development in Support of Safe Drug Design

      • Axel Pähler

      Pages 263-281

   9. In Vitro Assessment of Mitochondrial Toxicity to Predict Drug-Induced Liver Injury

      • Mathieu Porceddu, Nelly Buron, Pierre Rustin, Bernard Fromenty, Annie Borgne-Sanchez

      Pages 283-300

   10. Bile Salt Export Pump: Drug-Induced Liver Injury and Assessment Approaches

       • Ruitang Deng

       Pages 301-329

   11. High Content Screening for Prediction of Human Drug-Induced Liver Injury

       • Mikael Persson

       Pages 331-343

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-InducedLiver 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. 

• Acute liver failure
• Drug development
• Regulatory processes
• Preclinical and clinical studies
• Hepatotoxins
• Hepatotoxicity
• DILI

• Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, USA

  Minjun Chen

• Drug Safety Research and Development, Pfizer Inc., Groton, USA

  Yvonne Will

Policies and ethics