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Hepatotoxicity: Mechanisms of Liver Injury

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Liver Diseases

Abstract

Toxic liver disease, hepatotoxicity, encompasses numerous different individual diseases that ultimately lead to progressive damage of the liver, to liver malfunction and death. Environmental toxicity, alcoholic and non-alcoholic steatohepatitis, viral hepatitis, and cirrhosis are examples of liver diseases, though not reciprocally exclusive, that can ultimately lead to fatal liver disease. In young adults, there are several factors associated with risk of liver damage, including rising rates of obesity, excessive alcohol consumption, drugs of misuse alone or in combination with drugs of use. There is an urgent need to better understand the causes of this recent rise in fatal liver disease in a population that has not been at great risk previously.

Aims: The purpose of this chapter is to provide guidance to detection and assessment of hepatotoxicity induced by human health products, toxic environmental pollutants and plant and animal toxins. This paper is promoting the safe and effective use of therapeutic products by physicians, other health care professionals as well as patients. The knowledge is applicable to pharmaceutical products for human use, natural health products and biological drugs.

This chapter is intended to provide basic considerations for the detection requirements of hepatotoxicity caused by natural health products and pharmaceutical, both alone and in the presence of other health products, foods or xenobiotics.

The investigational approach used for a particular product will depend on multiple factors, including the pharmacodynamic and pharmacokinetic characteristics of the product, the indications, the dosages and routes of administration.

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Abbreviations

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase (glutamic-pyruvic transaminase, SGPT)

AST:

Aspartate aminotransferase (glutamic-oxaloacetic aminotransferases, SGOT)

CB:

Conjugated (direct) bilirubin

GGT:

γ-Glutamyltransferase (γ-glutamyltranspeptidase, GGTP)

ICH:

International Conference on Harmonisation

INR:

International Normalized Ratio

TB:

Total bilirubin (sum of conjugated and non-conjugated serum bilirubin)

ULN:

Upper limit of the normal reference range (or N)

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Acknowledgements

All the micrographs presented are cases that consulted Dr. Neuman and belong to In Vitro Drug Safety and Biotechnology.

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Authors and Affiliations

  1. In Vitro Drug Safety and Biotechnology, Department of Pharmacology and Toxicology, Banting Institute, University of Toronto, Toronto, ON, Canada

    Manuela G. Neuman

Authors
  1. Manuela G. Neuman
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Correspondence to Manuela G. Neuman .

Editor information

Editors and Affiliations

  1. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Florentina Radu-Ionita

  2. New Jersey Medical School, Rutgers University New Jersey Medical School, Newark, NJ, USA

    Nikolaos T. Pyrsopoulos

  3. Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Mariana Jinga

  4. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Ion C. Tintoiu

  5. Medical Radiation Sciences, Curtin University, Perth, WA, Australia

    Zhonghua Sun

  6. “Prof. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania

    Ecaterina Bontas

Self Study

Self Study

1.1 Questions and Answers

Which statement is true

  1. 1.

    Acetaminophen at therapeutic concentration taken concomitantly with alcohol in normal doses is

    1. (a)

      not harmful

    2. (b)

      a deadly combination

    Response correct (b)

  2. 2.

    In drug-induced hepatitis, which of the following is correct?

    1. (a)

      ALT is higher than AST

    2. (b)

      AST is higher than ALT

    Response correct (a)

  3. 3.

    Herbal and complementary medicine may produce:

    1. (a)

      Liver damage

    2. (b)

      Enhancement of liver function

    3. (c)

      Liver failure

    4. (d)

      All of the above

    Response correct (a)

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Neuman, M.G. (2020). Hepatotoxicity: Mechanisms of Liver Injury. In: Radu-Ionita, F., Pyrsopoulos, N., Jinga, M., Tintoiu, I., Sun, Z., Bontas, E. (eds) Liver Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-24432-3_7

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