DOI: 10.3390/healthcare14213720 ISSN: 2227-9032

Association Between Free Triiodothyronine and Metabolic Dysfunction-Associated Steatotic Liver Disease in Euthyroid Population: Evidence from NHANES 2007–2012

Tianru Zhang, Shiyu Peng, Ping He, Xinke Wang, Baoping Nie, Yuemin Feng, Zhen Yu, Qiang Zhu

Background/Objectives: This study investigated the associations of free triiodothyronine (FT3) with metabolic dysfunction-associated steatotic liver disease (MASLD) risk and high probability of advanced liver fibrosis in euthyroid individuals. Materials and Methods: We conducted a cross-sectional analysis of 6910 participants from the 2007–2012 cycles of the National Health and Nutrition Examination Survey (NHANES). MASLD was defined using the non-invasive Fatty Liver Index (FLI), and high probability of advanced liver fibrosis was evaluated by the Fibrosis-4 (FIB-4) score. Weighted multivariable logistic regression and restricted cubic spline (RCS) analyses were used to assess associations between serum FT3 and the two hepatic outcomes. Exploratory, unweighted mediation analyses examined whether serum albumin (ALB) or lymphocyte count (LYM) statistically accounted for part of the FT3–MASLD association. These analyses are hypothesis-generating, and causal mediation cannot be inferred from this design. Results: Higher FT3 was positively associated with FLI-defined MASLD (per 1 SD, 0.385 pg/mL: OR = 1.34, 95% CI 1.18–1.53, p < 0.001). In the primary fibrosis model without age adjustment, lower FT3 was associated with high probability of advanced liver fibrosis (OR = 0.41, 95% CI 0.26–0.65, p < 0.001), but after continuous age adjustment, this association attenuated and became non-significant. The ratio of free thyroxine to free triiodothyronine (FT4/FT3 ratio) was inversely associated with MASLD; its positive association with high probability of advanced liver fibrosis (from an age-unadjusted model) remains exploratory. Exploratory analyses suggested ALB and LYM might partly account for the FT3–MASLD association. Conclusions: In euthyroid adults, higher FT3 and a lower FT4/FT3 ratio were cross-sectionally associated with increased MASLD risk. Associations of lower FT3 and a higher FT4/FT3 ratio with high probability of advanced liver fibrosis were exploratory, age-dependent, and not robust. The fibrosis-related findings are cross-sectional associations and do not establish clinical utility.

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