Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans

Table 1

Examples of in vitro assays used in DILI prediction.

Cell model	Endpoints assessed	References
HepG2 cells	High content screening of cell viability	[61, 70, 119]
HepG2 cells	Mitochondrial injury	[78, 154]
Human liver-derived cell lines expressing human P450s	Cell viability	[63, 155–157]
Isolated primary human hepatocytes	High content screening of cell viability	[60, 158, 159]
Isolated primary rat hepatocytes	High content screening of cell viability	[49]
Isolated rat or human primary hepatocytes	Biliary efflux inhibition	[160–162]
HepaRG cells	High content screening of cell viability, BC dysfunction, intrahepatic cholestasis, cell viability, steatosis	[106, 163–165]
Membrane vesicle expressing bile salt export pump (BSEP)	BSEP activity inhibition	[19, 166, 167]
Isolated human primary hepatocytes	Covalent binding of radiolabeled compounds to proteins	[48, 168, 169]
Human hepatocytes plus cytokines	Cell viability	[130]
Hepatocytes (various species cocultured with nonparenchymal hepatic cells)	Liver cell viability and function	[29, 62]
Micropatterned human or rat hepatocyte/accessory cell cocultures	Cell viability function	[71]
Human liver microtissues	Cell viability	[30]
Human liver cell 3D microfluidic liver model	Cell toxicity (multiparametric)	[32]