Table 3.

Virus-driven liver disease studies with organoid models

Reference	Genetic disease	Culture approach	Study highlight
Nie et al. [130], 2018	HBV	Co-culture of PSC-derived hepatic endoderm with MSC and HUVEC	Parallel comparison of PSC-derived hepatocyte-like cells (HLCs) and liver organoids (LOs). LOs are more susceptible to HBV viral infection and could be maintained longer in culture compared to HLC.
			LO HBV models exhibit cytopathic effects of HBV infection.
De Crignis et al. [131], 2021	HBV	ICO culture	HBV-infected organoid models exhibit various disease hallmarks, including cccDNA formation and HBS antigen expression.
			HBV integration is detectable in the HBV patient-derived organoids and unique gene signatures identified in the transcriptome profiles of HBV patient-derived organoids is enriched in HBV and HCC patient tissue.
Li et al. [135], 2022	HEV	ICO culture	Patient-derived fetal and adult organoids can be employed for modeling HEV infection via overexpression of in vitro–transcribed genomic RNA.
			The organoid model was employed to demonstrate that HEV infects both cholangiocytes and hepatocytes, and viruses were released from the apical surface of both cell types.
			Small-scale antiviral drug screens with the HEV organoids identify Brequinar and Homoharringtonine as potential new HEV therapeutics.
a. Yang et al. [136], 2020	SARS-CoV-2	PSC-derived liver organoids	PSC-derived liver organoid was employed to demonstrate that SARS-CoV-2 virus can infect both hepatocytes and cholangiocyte .
b. Richards et al. [137], 2022			Single-cell transcriptome profiles of infected organoids show that the hepatocytes express higher levels of chemokines and cytokines than the cholangiocytesb.
a. Yang et al. [136], 2020	SARS-CoV-2	Intra-hepatic cholangiocyte organoids	ICO organoid-derived hepatocyte and cholangiocyte organoids can be infected with SARS-CoV-2 virus. Infection induces the expression of immune-related genes in both cell types.
b. Zhao et al. [138], 2020; Zhao et al. [139], 2023			SARS-CoV-2 virus infection results in the downregulation of genes encoding junction proteins and bile transporters in cholangiocyte organoidsa.
c. McCarron et al. [140], 2021			ICOs derived from Non-alcoholic steatohepatitis (NASH) patient have increased UBD expression, and exhibits increased sensitivity to SARS-CoV-2 virus infectionC.

HBV, hepatitis B virus; PSC, pluripotent stem cell; MSC, Mesenchymal Stem Cell; HUVEC, Human umbilical vein endothelial cell; ICO, intrahepatic cholangiocyte organoids; HBS, hepatitis B surface; HEV, hepatitis E virus.