Associations of metabolic dysfunction-associated steatotic liver disease and significant fibrosis phenotypes with...

To examine associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and significant fibrosis with glomerular hyperfiltration (GHF) defined from indexed estimated glomerular filtration rate (eGFR), accounting for body size.

We analyzed 9,140 NHANES participants and 721 adults from a Chinese clinical study. Liver phenotypes were G1 (no steatosis/no significant fibrosis), G2 (MASLD without significant fibrosis), and G3 (MASLD with significant fibrosis). Primary GHF was indexed eGFR above the survey-weighted age- and sex-specific 95th percentile of a low-risk NHANES reference, applied unchanged to both studies. BMI-adjusted Model 3 was central; metabolic adjustment and alternative GHF definitions were sensitivity analyses.

In NHANES Model 3, G2 and G3 had higher odds of GHF than G1 (OR 2.19, 95% CI 1.57-3.07; OR 2.46, 1.51-4.00), whereas G3 did not differ from G2 (OR 1.12, 0.74-1.70). In the identical fasting subsample, further metabolic adjustment attenuated G2 and G3 versus G1 (OR 1.94 and 2.08), while G3 versus G2 remained near the null. In China, G2 versus G1 was null, whereas G3 had higher odds than G1 and G2; however, G3 included only 29 participants and 8 events. NHANES findings were generally robust to indexed P90, age/sex/BSA-residual, and de-indexed sensitivity definitions.

In NHANES, MASLD phenotypes were associated with higher odds of GHF after accounting for body size, whereas significant fibrosis showed no clear incremental association beyond MASLD. The fibrosis-related association observed in the Chinese clinical study should be interpreted cautiously because of the small G3 subgroup and cross-population differences in GHF calibration. Prospective studies using measured GFR are needed to clarify the temporal and prognostic significance of GHF in MASLD.