Nonlinear Associations of Body Muscle-to-Fat Ratio With Long-Term Prognosis in MASLD.

BACKGROUND

As weight-loss therapies are increasingly incorporated into clinical practice for MASLD, assessing body composition has become increasingly important. Body muscle-to-fat ratio (BMFR) may provide an intuitive and integrated measure of body composition balance, but its association with long-term prognosis in MASLD remains unclear.

METHODS

We studied 83 006 UK Biobank participants with MASLD. BMFR was calculated as whole-body muscle mass divided by whole-body fat mass using bioelectrical impedance analysis. Restricted cubic spline, threshold-effect and two-piecewise Cox models assessed associations with liver-related events (LREs), cardiovascular events (CVEs), cardiovascular mortality and all-cause mortality, adjusting for BMI and other confounders.

RESULTS

BMFR showed significant non-linear associations with all outcomes. Sex-specific inflection points were identified for each outcome. For LREs, the thresholds were 2.82 in men and 1.45 in women; below these thresholds, each 1-SD increase in BMFR was associated with a lower risk of LREs (men: HR = 0.86, 95% CI: 0.75-0.98; women: HR = 0.72, 95% CI: 0.63-0.83), whereas above them it was associated with a higher risk (men: HR = 1.21, 95% CI: 1.07-1.36; women: HR = 1.33, 95% CI: 1.11-1.59). For CVEs, the thresholds were 2.03 in men and 1.48 in women; below these thresholds, each 1-SD increase in BMFR was associated with a lower risk in both sexes (men: HR = 0.77, 95% CI: 0.70-0.85; women: HR = 0.85, 95% CI: 0.81-0.89), whereas above them the association was not significant in men but was associated with a higher risk in women (HR = 1.19, 95% CI: 1.09-1.30). Cardiovascular mortality and all-cause mortality showed sex-specific non-linear patterns similar to those observed for CVEs.

CONCLUSIONS

In MASLD, BMFR was associated with liver-related and cardiovascular outcomes. Associations were generally U-shaped in women; in men, they were U-shaped for LREs and closer to L-shaped for cardiovascular outcomes and mortality. BMFR may provide complementary information on body composition beyond BMI. Further studies are needed to validate these exploratory findings.