Glucose–steatosis–fibrosis and glycemia–fibrosis scores in relation to mortality in NHANES 1999–2018

Abstract Glucose, hepatic steatosis, and fibrosis cluster across cardiovascular–kidney–metabolic (CKM) stages, but the incremental contribution of steatosis to mortality stratification is uncertain. We analyzed 21,511 adults from NHANES 1999–2018 linked to mortality through 2019. Missing covariates were multiply imputed (m = 50), scores and modified operational CKM stages were passively rederived, and survey-weighted Cox models were pooled across imputations. During follow-up, 3,317 all-cause and 1,056 cardiovascular disease (CVD) deaths occurred. Each 1-point higher glucose–steatosis–fibrosis (GSF) score was associated with all-cause mortality (HR 1.200, 95% CI 1.152–1.250) and CVD mortality (HR 1.273, 95% CI 1.197–1.355). However, steatosis was not independently associated with either outcome after conditioning on glycemia, fibrosis, and covariates. In the CKM common-complete internal benchmark, a simpler glycemia–fibrosis score performed at least as well as GSF for discrimination and Brier score. High versus low GSF corresponded to higher 10-year all-cause and CVD risks and shorter restricted mean survival. GSF therefore characterized population-level metabolic burden but did not demonstrate incremental predictive or clinical utility beyond glycemia and fibrosis.