The Obesity–MASLD–Myopenia Cascade: A Dynamic Loop within Metabolic Metamorphosis in Liver Disease
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Background & Aims
The metabolic interplay between obesity and myopenia (MP) in chronic liver disease (CLD) remains poorly understood. We investigated whether progressive liver dysfunction mediates an obesity–MASLD (metabolic dysfunction□associated steatotic liver disease)–MP cascade and assessed the prognostic impact of MP and myopenic obesity (MO) in advanced CLD (ACLD).
Methods
We analyzed 859 CLD patients cross□sectionally and 169 obese patients longitudinally (median 38□months), using multimodal MRI to measure liver stiffness (LS), proton□density fat fraction (PDFF), and body composition. Temporal relationships between changes (Δ) in adiposity, muscle mass, and liver injury markers were assessed. Prognosis in ACLD (n=328) was evaluated using Cox regression.
Results
MP and MO were present in 29% and 8% of patients, respectively. In the longitudinal cohort, MO prevalence increased significantly from 15% to 23% (P□<□0.01). In fibrosis stages F0–2, Δvisceral adipose tissue significantly correlated with ΔPDFF, ΔALT, and ΔLS (all P□<□0.01), whereas Δmuscle mass decreased, likely from weight loss. In F3–4, ΔALBI score and ΔPDFF (hepatic fat "burning□out") independently correlated with Δmuscle mass (both P□<□0.01). In ACLD, MP—but not obesity itself—was an independent predictor of liver□related death (HR□2.27, 95%□CI□1.08–4.78, P□=□0.025).
Conclusions
Our findings suggest an obesity–MASLD–MP cascade driven by a liver-centered metabolic paradox: preserved hepatic function promotes harmful fat accumulation, whereas hepatic dysfunction leads to fat depletion (energy deficiency) and muscle loss. Recognition of this dynamic loop highlights the need for stage-specific strategies: fat reduction initially, followed by aggressive muscle preservation and energy repletion in ACLD.
