Table 6.

Common hepatic in vitro models for drug toxicity studies.

Models	Cell Type/Culture Condition	Applications	Advantages	Disadvantages	Ref.
Hepatocyte sandwich culture	Hepatocytes (PHH)	A model to study hepatobiliary transportation and cholestasis (Drug-induced) liver injury	a) Maintenance of cell polarity and polygonal morphology b) Formation of functional bile canaliculi	a) Decreasing metabolic enzyme activity b) losing liver functionality, morphology and phenotype in long-term cultures	[162,163,167,168]
3D models	HepG2	Drug toxicity	a) Providing cell-cell interaction b) Maintenance of cell polarity c) Formation of functional bile canaliculi-like structures	a) Lack of many phenotypic and functional characteristics of the liver tissue	[169,170]
	HepaRG	Hepatotoxins screening A model to study drug-induced fibrosis	a) Formation of bile canaliculi-like structures b) Expression of functional bile acid transporters metabolic enzymes	a) Lack of many phenotypic and functional characteristics of the liver tissue	[171,172,173]
	Hepatocytes (PHH)	Drug toxicity assessments A model to chronic drug assessment	a) Increased CYPs activity b) Long term functionality	a) No bile canaliculi	[165,174,175]
	Stem cell-derived hepatocytes	Drug toxicity testing	a) Creating an accessible and useful model systems for viral and inherited metabolic disorders	a) Low expression of liver specific genes in metabolism b) Limited results regarding toxicology	[176]
Organ–on a chip platforms	Co–cultured Micro patterned cells	Drug toxicity tests	a) Preserved zonation b) Continuous perfusion of medium	Batch-to-batch variation of ECM substrates	[176,177,178]
	Perfused multiwall plate	Drug metabolism and drug toxicity assays	a) Facilitated nutrient exchange b) Efficient shear stress	a) Need more functional cells b) Consuming more culture media	[179,180]
	Microfluidic liver biochips	Toxicity assays	a) Facilitated nutrient exchange b) Efficient shear stress c) Mimicking in vivo environment, i.e., hexagonal structure	a) Complex system to establish and maintenance b) Sampling is difficult	[181,182]
3D bioprinting	3D liver bioprinting	Toxicity assays	a) Using bioink b) Sophisticated shaping	a) Complex system to establish and maintenance	[74,156]

CYPs, cytochromes P450.