Book ChapterDOI
Drug-induced liver injury.
Michael P. Holt,Changqing Ju +1 more
TLDR
It is hoped that this chapter will shed light on the major problems associated with DILI in regards to the pharmaceutical industry, drug regulatory agencies, physicians and pharmacists, and patients.Abstract:
Many drugs and environmental chemicals are capable of evoking some degree of liver injury. The liver represents a primary target for adverse drug reactions due to its central role in biotransformation and excretion of foreign compounds, its portal location within the circulation exposing it to a wide variety of substances, and its anatomic and physiologic structure. Drug-induced liver injury (DILI) remains the single most common adverse indication leading to drug candidate failure or withdrawal from the market. However, the absolute incidence of DILI is low, and this presents a challenge to mechanistic studies. DILI remains unpredictable making prevention very difficult. In this chapter, we focus on the current understanding of DILI. We begin with an overview regarding the significance and epidemiology of DILI and then examine the clinical presentation and susceptibility factors related to DILI. This is followed by a review of the current literature regarding the proposed pathogenesis of DILI, which involves the participation of a drug, or most often a reactive metabolite of the drug, that either directly affects cellular function or elicits an immune response. It is our hope that this chapter will shed light on the major problems associated with DILI in regards to the pharmaceutical industry, drug regulatory agencies, physicians and pharmacists, and patients.read more
Citations
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Journal ArticleDOI
Case definition and phenotype standardization in drug-induced liver injury
Guruprasad P. Aithal,Paul B. Watkins,Raúl J. Andrade,Dominique Larrey,Mariam Molokhia,Hajime Takikawa,Christine M. Hunt,Russell A. Wilke,Mark I. Avigan,Neil Kaplowitz,Einar Björnsson,Ann K. Daly +11 more
TL;DR: An international DILI Expert Working Group of clinicians and scientists reviewed current DILi terminology and diagnostic criteria so as to develop more uniform criteria that would define and characterize the spectrum of clinical syndromes that constitute D ILI.
Journal ArticleDOI
Endpoints and clinical trial design for nonalcoholic steatohepatitis.
Arun J. Sanyal,Elizabeth M. Brunt,David E. Kleiner,Kris V. Kowdley,Naga Chalasani,Joel E. Lavine,Vlad Ratziu,Arthur J. McCullough +7 more
TL;DR: This article summarizes the consensus arrived at a meeting of the American Association for the Study of Liver Diseases on the key endpoints and specific trial design issues that are germane for development of diagnostic biomarkers and treatment trials for NASH.
Journal ArticleDOI
ACG Clinical Guideline: The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury
Naga Chalasani,Paul H. Hayashi,Herbert L. Bonkovsky,Victor J. Navarro,William M. Lee,Robert J. Fontana +5 more
TL;DR: This ACG Clinical Guideline is presented an evidence-based approach to diagnosis and management of DILI with special emphasis on DILi due to herbal and dietary supplements and DilI occurring in individuals with underlying liver disease.
Journal ArticleDOI
Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease
Catherine C. Bell,Delilah F. G. Hendriks,Sabrina M. L. Moro,Ewa Ellis,Joanne Walsh,Anna Renblom,Lisa Fredriksson Puigvert,Anita C. A. Dankers,Frank Jacobs,Jan Snoeys,Rowena Sison-Young,Rosalind E. Jenkins,Åsa Nordling,Souren Mkrtchian,B. Kevin Park,Neil R. Kitteringham,Christopher E. Goldring,Volker M. Lauschke,Magnus Ingelman-Sundberg +18 more
TL;DR: It is demonstrated that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations, and the PHH spheroid system constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI.
Journal ArticleDOI
Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing
TL;DR: A nanosensor for rapid, real-time in vivo imaging of drug-induced ROS and RNS activity in the liver within minutes of drug challenge and its remediation longitudinally in mice after systemic challenge with acetaminophen or isoniazid is presented.
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Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States
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