Metabolic liver burden and osteoarthritis prevalence: A comparative analysis of noninvasive hepatic indices

Osteoarthritis (OA) is increasingly recognized as a condition with a distinct metabolic phenotype, characterized by systemic low-grade inflammation and metabolic dysregulation. Concurrent with the rising prevalence of OA is the global burden of metabolic dysfunction-associated steatotic liver disease. This study aimed to evaluate and compare the associations of 3 noninvasive liver scores - hepatic steatosis index (HSI), NAFLD fibrosis score (NFS), and Fibrosis-4 index (FIB-4) - with OA prevalence among US adults. We performed a cross-sectional analysis of National Health and Nutrition Examination Survey cycles (1999-2018). HSI, NFS, and FIB-4 were calculated and examined both as quartiles and per standard deviation increment. Associations with self-reported OA were estimated using survey-weighted modified Poisson regression with robust variance (prevalence ratios) as the primary approach, with survey-weighted logistic regression (odds ratios) performed as a secondary analysis. The final sample included 40,447 participants. In fully adjusted Poisson regression models (Model 3), HSI demonstrated the most robust and consistent association with OA. Participants in the highest HSI quartile exhibited a 2.09-fold higher OA prevalence compared with the lowest quartile, with a dose-response relationship. NFS demonstrated a moderate association, though substantially attenuated compared with its crude estimate after adjustment for demographic, socioeconomic, lifestyle, and non-embedded clinical covariates. Notably, the association between FIB-4 and OA was largely confounded by age; after adjustment, FIB-4 showed only a modest association in the highest quartile, whereas the continuous association was null. Sensitivity analyses consistently showed that HSI had the strongest and most stable association with OA among the 3 indices. The steatosis-oriented metabolic burden reflected by HSI shows a stronger adjusted association with OA than the more age-dependent fibrosis marker FIB-4 in the general population. These results support the view that steatosis-related metabolic dysfunction may be more relevant to OA burden than hepatic fibrotic burden alone. Because HSI incorporates body mass index and diabetes status, the observed association should be interpreted as that of a composite metabolic marker rather than a fully independent effect of hepatic steatosis itself. HSI may therefore be useful as a simple indicator of a steatosis-oriented metabolic OA profile in integrated risk assessment.