Red Cell Distribution Width as an Independent Prognostic Biomarker in MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) requires practical and inexpensive tools for risk stratification. We investigated whether the red cell distribution width (RDW), a routinely available hematologic parameter, predicts adverse clinical outcomes, using data from 352,623 UK Biobank participants, including 165,700 individuals with MASLD. RDW was analyzed as both a continuous and categorical variable using Cox proportional hazards models, restricted cubic splines, inverse probability treatment weighting, landmark, competing risk, and mediation analyses. Over a median follow-up of 13.6 years, each 1% increase in RDW was independently associated with higher risks of all-cause mortality (hazard ratio [HR] 1.14), cardiovascular disease (HR 1.07), cerebrovascular disease (HR 1.07), and chronic kidney disease (HR 1.09) (all p < 0.001). These associations remained consistent across multiple sensitivity analyses, and conventional biomarkers explained a modest proportion of the observed associations. Oxidative stress, together with other systemic processes affecting erythrocyte homeostasis, represents one potential mechanism underlying these associations. Higher RDW was independently associated with adverse clinical outcomes after adjustment for routine liver and metabolic biomarkers, supporting its potential value as a readily available prognostic marker in MASLD.