Hepatotoxicity

Hepatotoxicity
Other namessee below list
Drug-induced hepatitis with granulomata. Other causes were excluded with extensive investigations. Liver biopsy. H&E stain.
SpecialtyGastroenterology, Toxicology
ComplicationsCirrhosis, liver failure
Synonyms

Drug-induced liver injury (DILI)
Toxin-induced hepatitis
Drug-induced hepatitis
Drug-induced hepatic necrosis
Drug-induced hepatic fibrosis
Drug-induced hepatic granuloma
Toxic liver disease with hepatitis
Toxic liver disease with cholestasis
Toxic hepatitis
Toxic liver disease
Toxin-induced liver disease
Drug-induced liver disease
Drug-induced liver damage
Hepatogenous poisoning

Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.

The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. acetaminophen, paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., alpha-amanitin), and herbal remedies (two prominent examples being kava, though the causal mechanism is unknown, and comfrey, through pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins.

More than 900 drugs have been implicated in causing liver injury[1] (see LiverTox, external link, below) and it is the most common reason for a drug to be withdrawn from the market. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the need for toxicity prediction models (e.g. DTI),[2] and drug screening assays, such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process.[3] Chemicals often cause subclinical injury to the liver, which manifests only as abnormal liver enzyme tests.

Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures.[4][5]

  1. ^ Friedman SE, Grendell JH, McQuaid KR (2003). Current diagnosis & treatment in gastroenterology. New York: Lang Medical Books/McGraw-Hill. pp. 664–679. ISBN 978-0-8385-1551-8.
  2. ^ Dixit VA (March 2019). "A simple model to solve a complex drug toxicity problem". Toxicol Res. 8 (2): 157–171. doi:10.1039/c8tx00261d. PMC 6417485. PMID 30997019.
  3. ^ Greenhough S, Hay DC (2012). "Stem Cell-Based Toxicity Screening: Recent Advances in Hepatocyte Generation". Pharm Med. 26 (2): 85–89. doi:10.1007/BF03256896. S2CID 15893493.
  4. ^ McNally PF (2006). GI/Liver Secrets: with STUDENT CONSULT Access. Saint Louis: C.V. Mosby. ISBN 978-1-56053-618-5.
  5. ^ Ostapowicz G, Fontana RJ, Schiødt FV, Larson A, Davern TJ, Han SH, et al. (December 2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States". Ann Intern Med. 137 (12): 947–54. doi:10.7326/0003-4819-137-12-200212170-00007. PMID 12484709. S2CID 11390513.