TABLE 4.

Selected 3D viral hepatitis models established from different cell types.

Cell type	Culture paradigm	Culture period	Endpoints	Application	References
PHHs	MPCC co-culture	21 days	Expression of NTCP receptors	Disease modeling: HBV infection	Shlomai et al. (2014)
			Expression of HBsAg and HBcAg
			Expression of HBV DNA and replication intermediates
			Induced ISG gene expression
PHHs	Liver-on-a-chip mono-culture	22 days	Expression of HBsAg and HBcAg	Disease modeling: HBV infection	Ortega-Prieto et al. (2018)
			Expression of HBV DNA and replication intermediates
			Suppressed baseline innate immune activation
			Similar chemokine and cytokine responses as seen in HBV-infected patients
hiPSC-HLCs	Organoid co-culture	42 days	Expression of NTCP receptors	Disease modeling: HBV infection	Nie et al. (2018)
			Expression of HBV DNA and replication intermediates
			Expression of HBcAg and known infection-promoting factors
			Viral dose-dependent hepatic dysfunction

PHHs, primary human hepatocytes; hiPSCs, human induced pluripotent stem cells; HLCs, hepatocyte-like cells; NTCP, sodium-taurocholate co-transporting polypeptide; ISG, interferon-stimulated gene; MPCC, micropatterned co-culture; HBcAg, HBV core antigen.