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Review
. 2019 Mar 28;7(1):86-92.
doi: 10.14218/JCTH.2018.00042. Epub 2019 Mar 25.

Mechanisms of Hepatic Cholestatic Drug Injury

Tea Omanović Kolarić  1   2 , Vjera Ninčević  1   2 , Robert Smolić  1 , Martina Smolić  1   2 , George Y Wu  3
Affiliations
Review

Mechanisms of Hepatic Cholestatic Drug Injury

Tea Omanović Kolarić et al. J Clin Transl Hepatol. .

Abstract

Drug-induced cholestasis represents a form of drug-induced liver disease that can lead to severe impairment of liver function. Numerous drugs have been shown to cause cholestasis and consequently bile duct toxicity. However, there is still lack of therapeutic tools that can prevent progression to advanced stages of liver injury. This review focuses on the various pathological mechanisms by which drugs express their hepatotoxic effects, as well as consequences of increased bile acid and toxin accumulation in the hepatocytes.

Keywords: Bile acids; Cholestasis; Drug-induced liver injury.

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Conflict of interest statement

The authors have no conflict of interests related to this publication.

Figures

Fig. 1.
Fig. 1.. Localization of the most important hepatic transporters in hepatocytes.
Abbreviations: MRP3, multidrug resistance-associated protein 3; MRP4, multidrug resistance-associated protein 4; NTCP, sodium-taurocholate cotransporter; OATPs, organic anion transporting polypeptides; BSEP, bile salt export pump; MRP2, multidrug resistance-associated protein 2; MDR3, multidrug resistance protein-3; BCRP, breast cancer resistance protein; MDR1, multidrug resistance protein 1; OA, organic anion; BA-G, bile acid glucuronide; BA-S, bile acid sulfate; NA, sodium; BA, bile acid; OC, organic cation; PC, phosphatidylcholine.
See this image and copyright information in PMC

References

    1. Yang K, Köck K, Sedykh A, Tropsha A, Brouwer KL. An updated review on drug-induced cholestasis: mechanisms and investigation of physicochemical properties and pharmacokinetic parameters. J Pharm Sci. 2013;102:3037–3057. doi: 10.1002/jps.23584. - DOI - PMC - PubMed
    1. Padda MS, Sanchez M, Akhtar AJ, Boyer JL. Drug-induced cholestasis. Hepatology. 2011;53:1377–1387. doi: 10.1002/hep.24229. - DOI - PMC - PubMed
    1. Rabinowich L, Shibolet O. Drug induced steatohepatitis: An uncommon culprit of a common disease. Biomed Res Int. 2015;2015:168905. doi: 10.1155/2015/168905. - DOI - PMC - PubMed
    1. Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109:950–966. doi: 10.1038/ajg.2014.131. - DOI - PubMed
    1. Temple R. Hy’s law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf. 2006;15:241–243. doi: 10.1002/pds.1211. - DOI - PubMed