Comment on ‘Effect of Skeletal Muscle Mass and Its Associated Mediators on the Development of Steatotic Liver Disease: A Cohort Study in China’ by Liang et al.

We read with great interest the study by Liang et al. examining skeletal muscle mass indices and MASLD development 1. Their comprehensive analyses are impressive, yet the interpretation of skeletal muscle indices may warrant reconsideration. Table 1 of the original study reveals a notable pattern: MASLD patients have virtually identical absolute muscle mass (ASM/height2: 7.11 vs. 7.07 kg/m2) but substantially higher visceral adipose tissue (VAT = 84.6 vs. 114.4 cm2, +35%). The reversal of ASM/height2 from risk-increasing (RR 1.67) to risk-decreasing (RR 0.77) after BMI adjustment likely reflects the removal of adiposity confounding rather than revealing a true muscle effect. Non-SLD: 84.6 MASLD: 114.4 (+35%) Non-SLD: 0.084 MASLD: 0.062 (−26%) Expected: RR ≈ 1.0 (no effect expected) 2, 6 Expected: RR reduced to approximately 0.4–0.5 per SD increase 3, 4, 7 Table 1 of Liang et al.'s study shows that MASLD cases have substantially higher visceral fat area (VFA; 114.4 vs. 84.6 cm2, +35%), representing the largest between-group difference among body composition indices. Supplementary Figure S4 of the same study further demonstrates that higher VFA quartiles consistently confer greater MASLD risk across models 2. By contrast, Table S13 provides detailed per-standard-deviation risk estimates for multiple metabolic markers (e.g., BMI, HOMA-IR, triglycerides) but not for VFA, preventing direct quantification of its comparative predictive strength. Moreover, VFA was not included as a covariate in any multivariable model evaluating skeletal muscle indices (Tables 3, S6, S9–S11 and S15), making it impossible to determine whether the reported muscle effects are independent of visceral adiposity. The data are consistent with sarcopenic obesity—low muscle mass relative to adiposity. From the reported data, MASLD patients show a 26% lower ASM/VAT ratio (0.062 vs. 0.084), indicating insufficient muscle mass relative to their visceral adiposity burden. This single metric captures the essence of metabolic risk better than examining muscle or fat in isolation 3, 4. The authors' data strongly suggest that visceral adiposity is the primary driver of MASLD risk. The apparent associations with skeletal muscle mass indices likely reflect varying degrees of adiposity confounding rather than direct muscle–liver effects. Including VAT in future analyses would clarify whether skeletal muscle mass has protective effects independent of its correlation with visceral adiposity. Until VAT is incorporated into analytic models, the most parsimonious interpretation remains that the muscle-to-visceral-fat ratio—rather than muscle mass per se—defines metabolic risk in MASLD. This perspective does not diminish the clinical importance of maintaining muscle mass but rather emphasizes that interventions should target both muscle preservation and visceral fat reduction simultaneously 10. Importantly, this perspective aligns with recent MASLD clinical trials 11, in which GLP-1–based therapies markedly improve liver outcomes despite modest reductions in lean mass—reinforcing that it is the muscle-to-visceral-fat balance, rather than absolute muscle mass, that determines metabolic risk. The author has nothing to report. The author has nothing to report. The author declares no conflicts of interest.