Table 1.

Liver Diseases Modeled by iPSC-based Systems.

Disease	Configuration	Model Characteristics	Reference
Abetalipoproteinemia	2D culture	Decreased ApoB secretion, intracellular lipid accumulation, increased cell death	[70]
Alagille Syndrome	3D organoids containing hepatocytes and cholangiocytes	Impaired bile duct formation and regenerative capacity	[71]
	2D culture	Patient-derived, HLC phenotype uncharacterized	[72]
Alcohol-induced Liver Injury	2D culture	Reduced proliferation, oxidative mitochondrial injury, increased steatosis, and hepatocellular carcinoma markers	[66]
α-1 Antitrypsin Deficiency	2D culture	AAT retention, enrichment of fibrosis- and cirrhosis-associated pathways	[54]
Autosomal Recessive Hypercholesterolemia	2D culture	Reduced LDL uptake	[73]
Bile Salt Export Pump (BSEP) Deficiency	2D culture	Impaired biliary excretion, altered localization of BSEP protein	[74,75]
Biliary Atresia	2D culture	Decreased biliary marker expression, increased expression of fibrosis markers	[51,76]
Citrullinemia Type I	3D organoids	Accumulation of ammonia, decreased ureagenesis	[47]
	2D culture	Decreased ureagenesis	[77]
Familial Hypercholesterolemia	2D culture	Inability to uptake LDL	[60]
Hemophilia B	3D organoids	Production of inactive coagulation factor IX (F9)	[78]
	2D culture	Reduced expression and activity of F9	[58]
	2D culture	Aberrant splicing of F9 mRNA leading to reduced F9 expression	[79]
Hepatitis B	3D organoids	Higher susceptibility to HBV infection than 2D culture, increased duration of infectious virus production	[49]
	2D coculture of HLCs and liver non-parenchymal cells	Improved efficiency of infection relative to 2D monoculture due to epidermal growth factor (EGF) modulation of endocytosis	[50]
Hepatitis C	2D culture	Permissive to infection with HCV, upregulation of type I and III interferons in response to infection	[68]
	2D culture	Higher susceptibility to and propagation of HCV compared to Huh7 cells	[80]
	2D culture	Supportive of full HCV life cycle, increased expression of interferon-stimulated genes	[69]
Hepatitis E	2D culture	Permissive host for hepatitis E virus natural isolates	[67]
Malaria	2D culture	Permissive host for infection with Plasmodium species; chemical maturation allows for bioactivation of primaquine	[48]
mtDNA Depletion Syndrome	2D culture	Decreased mtDNA copy number, disruption of mitochondrial ultrastructure, reduced mitochondrial respiration/intracellular ATP, increased reactive oxygen species levels	[56]
	2D culture and 3D organoids	Decreased mtDNA, reduced mitochondrial respiration, increased reactive oxygen species, increased sensitivity to iron overload	[81]
Nonalcoholic Fatty Liver Disease	2D culture	Patient-specific lipid droplet formation upon administration of oleic acid, decreased lipid metabolism-associated gene expression in higher levels of steatosis	[82]
	2D culture	Decreased electron transport chain activity, altered transcription of mitochondrial respiration pathways, increased pyruvate carboxylase activity, and fumarate accumulation in response to steatosis induction	[83]
	2D culture	Defects in V-ATPase assembly leading to increased ApoB secretion	[84]
	3D organoids with hepatocytes, macrophages, mesenchymal stem cells, and endothelial cells	Spontaneous lipid accumulation in absence of fatty acid supplementation	[85]
Niemann–Pick Disease Type C (NPC)	2D culture	Increased lysosomal accumulation of cholesterol, increased trafficking of NPC1 to lysosomes	[86]
	2D culture	Increased lysosomal cholesterol accumulation, increased cell size, upregulated autophagy and impaired autophagic flux	[87]
Ornithine Transcarbamylase Deficiency	2D culture	Decreased urea secretion	[88]
Pompe Disease	2D culture	Accumulation of glycogen in lysosomes	[65]
Primary Sclerosing Cholangitis	3D organoids containing cholangiocytes	Altered organoid morphology, increased cellular senescence and inflammatory cytokine secretion	[44]
Propionic Acidemia	2D culture	Knockout of propionyl CoA carboxylase	[89]
Transthyretin (TTR) Amyloidosis	2D culture	Secretion of abnormal TTR, increased expression of transferrin and unfolded protein response signaling pathways	[90,91]
Wilson Disease	2D culture	Patient-derived, HLC phenotype uncharacterized	[92]
	2D culture	Increased trafficking of ATP7B to the Golgi complex, increased rate of ATP7B degradation	[93]
Zellweger Spectrum Disorder	2D culture	Defective peroxisome assembly	[94]