Liver fibrosis, but not steatosis, provides incremental prognostic value beyond cardiovascular-kidney-metabolic staging.

BACKGROUND AND AIMS: Cardiovascular-kidney-metabolic (CKM) syndrome reflects systemic cardiometabolic risk, but whether hepatic steatosis or fibrosis provides incremental prognostic information beyond CKM staging remains unclear. We evaluated the prognostic contributions of steatosis- and fibrosis-based hepatic phenotypes across CKM stages.

METHODS AND

RESULTS

This prospective cohort study included 602,885 adults undergoing health screening between 2005 and 2022 in the Kangbuk Samsung Health Study. CKM stage was classified according to the 2023 American Heart Association criteria. Hepatic steatosis was assessed using ultrasonography-defined fatty liver and metabolic dysfunction-associated steatotic liver disease, whereas hepatic fibrosis was assessed using the fibrosis-4 (FIB-4) index. During a median follow-up of 7.4 years, advancing CKM stage was associated with progressively higher risks of all-cause, cardiovascular, and liver-related mortality. Compared with CKM stage 0, CKM stage 3 was associated with increased risks of all-cause mortality (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.82-2.42) and cardiovascular mortality (HR, 3.28; 95% CI, 2.20-4.88), while CKM stage 4 showed the highest cardiovascular mortality risk (HR, 4.69; 95% CI, 3.03-7.26). These associations remained robust after adjustment for hepatic phenotypes. Adding steatosis-based phenotypes produced minimal improvement in risk discrimination beyond CKM staging. In contrast, adding FIB-4 improved prediction of liver-related mortality, increasing the C statistic from 0.8672 to 0.8972 with a categorical net reclassification improvement of 0.610 (95% CI, 0.556-0.665).

CONCLUSIONS

CKM staging captured most systemic cardiometabolic mortality risk, whereas hepatic fibrosis, but not steatosis, provided additional prognostic information for liver-related mortality.