The importance of serum ferritin has been demonstrated in many liver diseases, but its relationship with liver stiffness remains unclear. The objective of this study was to investigate the association between serum ferritin levels and participants' liver stiffness measurement (LSM) in the United States population. We conducted a screening of participants from National Health and Nutrition Examination Survey (NHANES) 2017.1 to 2020.3 to ensure that participants included in this study had complete serum ferritin and LSM information. Association between the independent variable (serum ferritin) and the dependent variable (LSM) was investigated by multiple linear regression and subgroup analysis was performed to identify sensitive individuals, and we subsequently assessed whether there was a non-linear relationship between the 2 using smoothed curve fitting and threshold effect models. The final 7143 participants were included in this study. There was a positive association between participants' serum ferritin concentration and LSM, with an effect value of (β = 0.0007, 95% confidence interval (CI): 0.0002-0.0011) in the all-adjusted model. The smoothing curve and threshold effect models indicated a non-linear positive correlation between serum ferritin and LSM, which was more pronounced when serum ferritin concentration exceeded 440 ng/mL. Subsequent subgroup analysis showed that this positive correlation was more pronounced in males (β = 0.0007, 95% CI: 0.0001-0.0012), age >60 years (β = 0.00015, 95% CI: 0.0007-0.0023), black participants (β = 0.00018, 95% CI: 0.0009-0.0026), and participants with body mass index (BMI) <25 kg/m2 (β = 0.00012, 95% CI: 0.0005-0.0020). In U.S. adults, there was a positive correlation between serum ferritin levels and liver stiffness, which was more pronounced when serum ferritin exceeded 440 ng/mL. Our study suggested that regular serum ferritin testing would be beneficial in monitoring changes in liver stiffness. Male, age >60 years, black participants, and those with a BMI < 25 kg/m2 should be of greater consideration.

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