Treatment response in pediatric metabolic dysfunction-associated steatotic liver disease: Noninvasive endpoints and body composition

Table 2 Three-tier, treatment-aware framework for response assessment in pediatric metabolic dysfunction-associated steatotic liver disease

Tier	Purpose and setting	Core domains	Suggested measures	Timing	Interpretation principles
Tier 1: Minimum clinical assessment	All care settings; establish direction, safety, and treatment exposure	Treatment/adherence; growth-adjusted adiposity; biochemical injury; cardiometabolic health; growth/puberty; safety; patient priorities	Treatment dose/exposure; height and growth velocity; %BMIp95 or BMI trajectory; ALT, AST, GGT; glucose/HbA1c, lipids, blood pressure; symptoms, quality of life, burden, physical function	Baseline; approximately 8-12 weeks after major change; then every 3-6 months during active treatment	Report achieved value, absolute change, relative change, and threshold crossing separately. Do not label normal ALT as histological remission. Evaluate alternative causes and access barriers
Tier 2: Specialist-center assessment	Clarify steatosis/fibrosis risk, discordance, or tissue consequences when results will change care	Quantitative steatosis; stiffness; standardized body composition and function; modality-specific safety	MRI-PDFF when available; MRE or standardized VCTE; BIA or DXA plus handgrip/functional assessment; nutrition and bone assessment after surgery	MRI-PDFF approximately 6-12 months after intensive intervention; elastography approximately 12-24 months in stable care; individualized sooner for high risk	Use the same scanner/device/probe and standardized fasting/quality criteria. Interpret liver fat, stiffness, adiposity, and muscle as separate axes. Adult thresholds are not automatically pediatric thresholds
Tier 3: Research endpoints	Trials and mechanistic cohorts; validate meaningful longitudinal change and core outcomes	Histology; advanced imaging; serum/molecular biomarkers; direct muscle measures; standardized patient-reported outcomes; feasibility and equity	Paired biopsy when ethically justified; centralized imaging; ELF, PRO-C3, cytokeratin-18 or omics; D3-creatine or detailed DXA; prespecified quality-of-life and treatment-burden instruments	Prespecified by biological timescale and intervention; generally 6-24 months with repeated exposure and safety measures	Anchor change to histology, function, clinical risk, or patient-important benefit; quantify measurement error and missingness; validate across puberty, treatment modalities, and diverse populations

BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; HbA1c: Glycated hemoglobin; MRI-PDFF: Magnetic resonance imaging proton density fat fraction; MRE: Magnetic resonance elastography; VCTE: Vibration-controlled transient elastography; BIA: Bioelectrical impedance analysis; DXA: Dual-energy X-ray absorptiometry; ELF: Enhanced liver fibrosis; PRO-C3: N-terminal pro-peptide of type III collagen; D3-creatine: Deuterated-creatine dilution.