Fighting the epidemic of pediatric metabolic dysfunction-associated steatotic liver disease: Role of non-invasive diagnostics and early pharmacological intervention

Table 1 Diagnostic accuracy of non-invasive diagnostics in pediatric metabolic dysfunction-associated steatotic liver disease

Diagnostic		Sensitivity	Specificity	AUROC	Comparison	Ref.
Serum ALT ≥ 50 (boys) ≥ 44 (girls) in overweight children ≥ 10 years		0.88	0.26	-	Biopsy-proven NAFLD	Schwimmer et al[28], 2013
Serum ALT ≥ 80 in overweight children ≥ 10 years		0.57	0.71	-	Biopsy NAFLD	Schwimmer et al[28], 2013
		0.61	0.62	-	Biopsy NASH
		0.76	0.59	-	Biopsy advanced fibrosis
Serum ALT ≥ 26 (boys) ≥ 22 (girls)		0.53	0.69	0.66	Ultrasound-detected steatosis + metabolic risk factors	Di Bonito et al[21], 2025
PNFS		0.97 (cutoff > 8%)	0.33 (cutoff > 8%)	0.74	Biopsy (advanced fibrosis ≥ F3)	Alkhouri et al[20], 2014
Ultrasonography		0.60-0.65	-	-	Biopsy mild steatosis (5%-33%; adult data)	Ferraioli et al[22], 2019
		0.84	0.93	0.93	Moderate-severe steatosis (20%-30%; adult data)	Hernaez et al[23], 2011
TE-CAP		0.86	0.88	0.94	Biopsy/MRS S1-S3 steatosis	Jia et al[25], 2021
TE-CAP		0.89	0.90	0.95	Biopsy, imaging or MRI-PDFF	Xu et al[29], 2025
TE-LSM	> 7.4 kPa	1.00	0.92	0.99	Biopsy-proven significant fibrosis (≥ F2)	Nobili et al[26], 2008
	> 10.2 kPa	1.00	1.00	1.00	Biopsy: Advanced fibrosis (≥ F3)
	> 8.5 kPa	0.72	0.62	0.76	Advanced liver disease on biopsy (MASLD subset of larger pediatric cohort of CLD)	Jarasvaraparn et al[24], 2025
MR elastography (cut-off 3.05 kPa)		0.50	0.92	0.92	Biopsy (advanced fibrosis ≥ F3 vs F0-F2)	Schwimmer et al[27], 2017
MRI-PDFF		0.95	0.92	0.96	Biopsy/MRS S1-S3 steatosis	Jia et al[25], 2021

ALT: Alanine aminotransferase; AUROC: Area under receiver operating characteristic curve; CLD: Chronic liver disease; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; TE-CAP: Transient elastography-controlled attenuation parameter; TE-LSM: Transient elastography-liver stiffness measurement; MRI-PDFF: Magnetic resonance imaging-proton density fat fraction; MRS: Magnetic resonance spectroscopy; PNFS: Pediatric non-alcoholic fatty liver disease fibrosis score; MASLD: Metabolic dysfunction-associated steatotic liver disease.<br/>.

Table 2 Summary of studies on pharmacotherapy for pediatric metabolic dysfunction-associated steatotic liver disease

Medication class	Study design & population	Primary endpoint	Efficacy summary	Safety/adverse events	Ref.
GLP-1RA (liraglutide, semaglutide)	Retrospective cohort, n = 42, age ≤ 18 years, MASLD diagnosis, GLP-1RA prescribed for obesity or T2DM[1]	ALT reduction at 6 months and end-of-treatment	Significant mean ALT reduction (-56 U/L at 6 months, -37 U/L at EOT, P < 0.05); greater effect in T2DM; improvements in AST, GGT, HbA1c, triglycerides; BMI stabilization, not reduction	Mild-moderate GI symptoms (nausea, vomiting, diarrhea); no serious adverse events reported	Tou and Panganiban[72], 2025
Metformin	Meta-analysis	ALT reduction	No significant improvement in ALT	GI upset, rare lactic acidosis	Gkiourtzis et al[62], 2023
Lifestyle/standard of care	Longitudinal cohort, n = 440, pediatric MASLD	Composite improvement (ALT, GGT, histology)	22% improved at 1 year, 31% at 2 years; 20% worsened; BMI and cholesterol changes most associated with outcomes	Not applicable	Newton et al[82], 2025
Resmetirom	No pediatric studies to date

GLP-1RA: Glucagon-like peptide 1 receptor agonists; T2DM: Type 2 diabetes mellitus; ALT: Alanine aminotransferase; GGT: Gamma glutamyl transferase; HbA1c: Glycated hemoglobin; BMI: Body mass index; GI: Gastrointestinal; MASLD: Metabolic dysfunction-associated steatotic liver disease.