Howell, LS
(2019)
The role of cholangiocytes in the prediction and detection of drug-induced liver injury.
PhD thesis, University of Liverpool.
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Abstract
Drug-induced liver injury (DILI) is a leading cause of drug attrition throughout all stages of the drug discovery process and is a frequent adverse drug reaction (ADR) with significant clinical burden. Therefore, a concerted effort to predict the onset of DILI before clinical manifestation is paramount. Nevertheless, currently available models to predict DILI are often lacking, due to their poor physiological relevancy to the in vivo hepatic phenotype. Furthermore, the current gold standard biomarkers for diagnosing DILI, such as alkaline phosphatase (ALP), have inadequate sensitivity and specificity. Whilst circulating levels of miR-122 have shown improved clinical utility in diagnosing hepatocellular DILI, miRNAs signatures for other hepatic cell types have not yet been elucidated. Cholangiocytes are epithelial cells that line the hepatic bile ducts and are primarily responsible for altering the composition of canalicular bile. Cholangiocytes are targeted by both mixed and cholestatic DILI, which without proper diagnosis and clinical intervention, can cause bile duct degeneration and destruction. Cholangiocyte DILI is typically diagnosed by elevations in circulating ALP, though it is not known if a panel ... (continues)
| Item Type: | Thesis (PhD) |
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| Divisions: | Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 Jan 2020 16:47 |
| Last Modified: | 03 Apr 2025 04:56 |
| DOI: | 10.17638/03061355 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3061355 |
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