Thyroid Hormone Sensitivity Linked to NAFLD Risk and Liver Fibrosis Progression: Study Finds

"A higher FT3/FT4 ratio was associated with an increased risk of developing NAFLD (OR 1.45) and greater severity of liver fibrosis (ORs 3.21–10.80), highlighting the potential role of thyroid hormones in the progression of NAFLD," the researchers reported in Diabetes, Metabolic Syndrome and Obesity.

The researchers note that non-alcoholic fatty liver disease is the most prevalent chronic liver disorder, often linked to metabolic conditions like obesity and diabetes. Research suggests thyroid hormone resistance may play a role in NAFLD progression. Recent studies highlight associations between thyroid sensitivity indices, NAFLD risk, and advanced liver fibrosis in euthyroid individuals.

Against the above background, Liyuan Zhou, Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China, and colleagues aimed to explore the relationship between thyroid hormone sensitivity, NAFLD risk, and the progression of liver fibrosis in euthyroid individuals.

For this purpose, the researchers recruited 29,386 adult participants from the medical examination center of Beijing Chao-Yang Hospital. They assessed thyroid hormone sensitivity using various indices, including FT3/FT4 ratio, TFQIFT4, TFQIFT3, TSHI, TT4RI, and TT3RI. Logistic regression analysis examined the association between these indices and NAFLD risk, along with related metabolic disorders. Additionally, ordinal logistic regression was employed to evaluate the correlation between thyroid hormone sensitivity and liver fibrosis severity using noninvasive fibrosis indices.

The key findings of the study were as follows:

• Euthyroid adults with NAFLD exhibited elevated serum FT3 and FT4 levels, reduced TSH, and impaired thyroid hormone sensitivity.
• The risk of NAFLD was significantly higher in individuals in the fourth quartile of TFQIFT3 (OR 1.25) and FT3/FT4 (OR 1.45) compared to those in the first quartile, even after adjusting for metabolic confounders.
• Among NAFLD patients, higher FT3/FT4 levels were positively associated with greater liver fibrosis severity.
• The odds ratios per standard deviation increase in FT3/FT4 were 10.80 for the aminotransferase-to-platelet ratio index, 4.74 for the NAFLD fibrosis score, and 3.21 for the fibrosis-4 index.

"Reduced central sensitivity to FT3 and elevated FT3/FT4 levels were associated with a higher risk of NAFLD and related metabolic disorders. Moreover, higher FT3/FT4 was linked to increased liver fibrosis severity in NAFLD patients. These thyroid hormone sensitivity indices may aid in assessing and monitoring NAFLD risk and fibrosis progression," the researchers concluded.

Reference:

Zhou L, Jiang L, An Y, Liu J, Wang G, Wang Y, Yang N. Association of Sensitivity to Thyroid Hormones and Non-Alcoholic Fatty Liver Disease and the Severity of Liver Fibrosis in Euthyroid Adults: A Retrospective Study. Diabetes Metab Syndr Obes. 2025;18:479-490. https://doi.org/10.2147/DMSO.S499517