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Drug Induced Liver Injury: Mechanisms, Diagnosis, and Clinical Management

  • Rolf Teschke
  • Gaby Danan
Chapter

Abstract

Similarly to other chemicals such as alcohol and solvents, drugs can injure the liver. A body of evidence suggests that mechanisms for drug induced liver injury (DILI) may follow a three-step cascade of events: drugs or their metabolites cause cell stress directly or through reactive oxygen species (ROS) during drug oxidation via cytochrome P450, impair mitochondrial functions, trigger immune reactions, and impair mitochondrial functions that would initiate apoptosis or necrosis leading to cell death. Clinically, toxicity DILI commonly refers to the idiosyncratic toxicity that occurs at therapeutic doses, affects a few susceptible individuals, and is not predictable. Conversely, intrinsic toxicity is dose dependent and thus predictable in individuals given an overdose of certain drugs such as acetaminophen. The diagnosis of DILI is based on timing of the events and the exclusion of alternative causes, and both require a quantitative scoring causality assessment method (CAM) such as RUCAM (Roussel Uclaf Causality Assessment Method), resulting in causality levels of highly probable, probable, possible, unlikely or excluded. For DILI characterization, only cases with a highly probable or probable causality grading should be used. Beside the product information, DILI databases and review articles should be consulted to help identify the offending drugs. Cessation of the suspected drug and symptomatic treatment commonly lead to a favorable outcome. N-acetylcysteine is the best treatment to prevent aggravation of DILI due to overdosed acetaminophen. In rare instances, DILI progresses in few days or weeks to acute liver failure requiring liver transplantation.

Keywords

Drug induced liver injury DILI Idiosyncratic DILI Intrinsic DILI Roussel Uclaf Causality Assessment Method RUCAM Herb induced liver injury HILI Reactive oxygen species 

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Further Reading

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Related Links/Journals/Book

  1. Teschke R, Andrade RJ. Special issue “Drug, herb, and dietary supplement hepatotoxicity”. Int J Mol Sci. 2016;17(9):1488.  https://doi.org/10.3390/ijms17091488. Available at: http://www.mdpi.com/journal/ijms/special_issues/Hepatotoxicity. Last accessed July 1, 2018CrossRefPubMedCentralGoogle Scholar
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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Rolf Teschke
    • 1
  • Gaby Danan
    • 2
  1. 1.Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Hanau, Academic Teaching Hospital of the Medical FacultyGoethe University Frankfurt/MainFrankfurt/MainGermany
  2. 2.Pharmacovigilance ConsultancyParisFrance

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