Organoids as preclinical platforms for metabolic dysfunction-associated steatotic liver disease: Model construction, mechanistic dissection, and therapeutic translation

Table 3 Identification of potential metabolic dysfunction-associated steatotic liver disease biomarkers using liver organoid models

Biomarker	Cellular origin	Model	Expression	Function/Description	Ref.
26-hydroxycholesterol	hiPSCs	250 μM OA, 250 μM PA, 10 mmol/L fructose for 48 hours	Upregulated	26-hydroxycholesterol exerts an anti-inflammatory signal on quiescent HSCs	Kømurcu et al[27], 2023
ADGRG1	hPSCs	500 μM OA/500 μM PA/10 ng/mL TGF-β1 for 4 days	Upregulated	The transcriptional profile of ADGRG1 is upregulated in cells of the fibrotic and inflammatory niche in response to injury	Pirola et al[29], 2026
lncRNA ENSMUST00000244884	Primary biliary duct-derived LOs from mice liver tissue	2/10 ng/mL FSH for 48 hours	Upregulated	Knocking down this long non-coding RNA promotes liver cholesterol excretion and accelerating lipid metabolism	Yu et al[42], 2026
Tryptophan-derived metabolites	Primary ductal organoids-derived LOs from mice liver tissue	200 μM OA and 100 μM PA for 3 days	Upregulated	Tryptophan-derived metabolites promote lipid droplet formation and enhance the inflammatory response	Zhan et al[46], 2025
sCD46	Human liver tissue	2 mmol/L FFA (OA:PA = 2:1) for 24 hours	Upregulated	Lipid accumulation in human hepatocytes reduces cell-surface CD46 via matrix metalloproteinases, thereby releasing sCD46 and promoting the differentiation of IL-4+ iNKT cells	Bitterer et al[54], 2024
CES1/IL18R1	Harbor residential bipotent progenitor cells from human liver tissue	Lactate/pyruvate/octanoic acid (10:1:2 mM; 15:1.5:3 mM) for 96 hours	Upregulated	CES1, IL-18R1: Population-based proteomics biomarkers validated in human LOs for MASLD/fibrosis	Abozaid et al[55], 2023
HAMP1	Human liver tissue	400 μM OA and 200 μM PA	Upregulated	Elevated pre-treatment HAMP1 predicts better response to saponin therapy in MASLD, and reduced HAMP1 post-treatment links to histological improvement	Kim et al[62], 2025

hiPSCs: Human induced pluripotent stem cells; OA: Oleic acid; PA: Palmitic acid; HSC: Hepatic stellate cell; ADGRG1: Adhesion G-protein-coupled receptor G1; hPSCs: Human pluripotent stem cells; TGF-β: Transforming growth factor-β; LO: Liver organoid; sCD46: Soluble CD46; FSH: Follicle-stimulating hormone; FFA: Free fatty acids; iNKT: Invariant natural killer T; CES1: Carboxylesterase 1; IL18R1: Interleukin-18 receptor 1; MASLD: Metabolic dysfunction-associated steatotic liver disease; HAMP1: Hepcidin antimicrobial peptide 1.