High TSH Levels Associated With Advanced Hepatic Fibrosis

Thyroid function is considered one of the most important risk factors for its prominent effects on hepatic fatty acid and cholesterol synthesis.

Low-normal thyroid function is associated with an increased risk for advanced hepatic fibrosis in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), according to study results published in BMC Gastroenterology.

Researchers examined the data of patients who underwent abdominal ultrasonography and thyroid function examination at a hospital in Shanghai, China, from 2015 to 2021.

The probability of advanced fibrosis was estimated with use of the fibrosis-4 index (FIB-4) and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). A FIB-4 score of under 1.30 and/or a NFS score of under -1.455 were used to exclude patients with MAFLD who had advanced fibrosis, and a FIB-4 score of more than 2.67 and/or a NFS score of more than 0.676 were used to identify those who had advanced fibrosis of fatty liver disease (FLD).

Thyroid function parameters such as thyroid-stimulating hormone (TSH), free thyroxine, and thyroxine levels were analyzed, and plasma thyroid hormone levels were measured. The participants were categorized into 3 groups based on TSH levels. Strict-normal thyroid function was defined as 0.35 to 2.5 mIU/L, low-normal thyroid function was defined as 2.5 to 4.5 mIU/L, and subclinical hypothyroidism [SCH] was defined as under 0.45 mIU/L.

A total of 19,946 participants (mean age, 47.31 years; 52.78% men; 27.55% with MAFLD) were included. Of the cohort, 14,789 individuals (74.15%) had strict-normal thyroid function and 5157 (25.85%) had low thyroid function, of which the latter group was further subclassified into 4328 with low-normal thyroid function (21.70%) and 829 with SCH (4.15%).

Our findings provide clues that elevated TSH within the normal range may also increase the risk for advanced fibrosis in patients with MAFLD, which has implications for clinical practice and public health.

Participants with low thyroid function had a higher proportion of advanced fibrosis compared with those with strict-normal thyroid function (FIB-4 >2.67: 6.48% vs 3.39%; NFS >0.676: 3.41% vs 1.63%). In participants who had low thyroid function, FIB-4 scores of less than 1.30 (52.16% vs 37.91%) and NFS scores of less than -1.455 (41.81% vs 32.09%) were more common in participants with SCH vs low-normal thyroid function.

Univariable regression did not identify a significant association between thyroid dysfunction and risk for MAFLD. After adjustment for age and sex, logistic regression analysis demonstrated that low-normal thyroid function increased the risk for MAFLD (odds ratio [OR] 1.09; 95% CI, 1.01-1.18). The significant association between low-normal thyroid function and MAFLD was not evident in the multivariable regression model further adjusted for body mass index (BMI), type 2 diabetes, and hypertension.

In univariable regression analysis, SCH and low-normal thyroid function were associated with FIB-4 scores under 1.30 (low-normal: OR 1.45; 95% CI, 1.27-1.66; SCH: OR 2.59; 95% CI, 1.99-3.39) and NFS scores under -1.455 (low-normal: OR 1.41; 95% CI, 1.23-1.62; SCH: OR 2.15; 95% CI, 1.63-2.81). These associations were not observed in the multivariable regression model after adjustment for covariates.

In multivariable regression analysis, low-normal thyroid function significantly increased the risk for advanced fibrosis in patients with MAFLD after adjusting for age, sex, BMI, type 2 diabetes, and hypertension (FIB-4 >2.67: OR 1.41; 95% CI, 1.02-1.93; NFS >0.676: OR 1.72; 95% CI, 1.08-2.72).

The study was limited by the fact that that FLD was diagnosed with ultrasonography, and advanced fibrosis was determined by noninvasive fibrosis score. Selection bias may have occurred in the patients who had thyroid testing, and the analysis did not assess C reactive protein, waist circumference, and insulin resistance.

“Our findings provide clues that elevated TSH within the normal range may also increase the risk of advanced fibrosis in patients with MAFLD, which has implications for clinical practice and public health,” conclude the study authors.

This article originally appeared on Gastroenterology Advisor


Fan H, Li L, Liu Z, et al. Low thyroid function is associated with an increased risk of advanced fibrosis in patients with metabolic dysfunction-associated fatty liver disease. BMC Gastroenterol. Published online January 5, 2023. doi:10.1186/s12876-022-02612-3