Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity

. 2023 Nov 20:1926233231212255.

doi: 10.1177/01926233231212255.

Online ahead of print.


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Chitra Saran et al.

Toxicol Pathol.



Drug-induced liver injury (DILI) remains a major concern in drug development from a patient safety perspective because it is the leading cause of acute liver failure. One mechanism of DILI is altered bile acid homeostasis and involves several hepatic bile acid transporters. Functional impairment of some hepatic bile acid transporters by drugs, disease, or genetic mutations may lead to toxic accumulation of bile acids within hepatocytes and increase DILI susceptibility. This review focuses on the role of hepatic bile acid transporters in DILI. Model systems, primarily in vitro and modeling tools, such as DILIsym, used in assessing transporter-mediated DILI are discussed. Due to species differences in bile acid homeostasis and drug-transporter interactions, key aspects and challenges associated with the use of preclinical animal models for DILI assessment are emphasized. Learnings are highlighted from three case studies of hepatotoxic drugs: troglitazone, tolvaptan, and tyrosine kinase inhibitors (dasatinib, pazopanib, and sorafenib). The development of advanced in vitro models and novel biomarkers that can reliably predict DILI is critical and remains an important focus of ongoing investigations to minimize patient risk for liver-related adverse reactions associated with medication use.


Hepatic transporters; bile acids; drug-induced liver injury; hepatotoxicity; kinase inhibitors; tolvaptan; troglitazone.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Prof. KLRB is a coinventor of the sandwich-cultured hepatocyte technology for quantification of biliary excretion (B-CLEAR) and related technologies, which have been licensed exclusively to BioIVT.

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