Identifying the association between hemoglobin levels and metabolic dysfunction-associated steatotic liver disease: An observational study and Mendelian randomization analysis.

Observational studies suggest a relationship between hemoglobin (Hb) levels and metabolic dysfunction-associated steatotic liver disease (MASLD), but its specific nature remains unclear. This study aimed to clarify the association through a National Health and Nutrition Examination Survey (NHANES) cross-sectional analysis and a 2-sample Mendelian randomization (MR) approach. We utilized NHANES data from 49,693 participants (2009-2018). Weighted multivariate logistic regression examined the Hb-MASLD association, with smoothed curve fitting and threshold effect analysis exploring nonlinear relationships. MR analyses assessed the observed causal relationship. Among 6165 NHANES participants, higher Hb levels were positively associated with MASLD risk (odds ratio = 1.15, 95% confidence interval = 1.08-1.23). Notably, when Hb concentrations exceeded 12.9 g/dL, MASLD risk significantly increased (odds ratio = 1.25, 95% confidence interval = 1.18-1.32). Two-sample MR analysis supported a causal relationship between elevated Hb levels and increased MASLD risk. Sensitivity analyses confirmed robustness (all P > .05). This study demonstrates that higher Hb levels are associated with an increased risk of MASLD, revealing potential nonlinear trends. MR analysis further confirmed this causal relationship, suggesting Hb levels could be a target for early intervention in preventing MASLD. These findings underscore the need for additional research to explore Hb's role in MASLD development and to inform clinical guidelines.