Spotlight On Thyroid Function In Liver Disease Patients
Overview
In a recent study, researchers investigated the relationship between low thyroid function and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a term coined to emphasize the role of cardiometabolic dysfunction in liver disease. The study, conducted as a retrospective cohort study from 2016 to 2021 with 2901 participants, aimed to explore this association within this evolving framework.
Participants were categorized into two groups based on their initial thyroid stimulating hormone (TSH) levels: those with strict-normal thyroid function and those with low thyroid function (including low-normal thyroid function and subclinical hypothyroidism). Cox regression models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Over a median follow-up period of 15.6 months, 165 (8.9%) participants with strict-normal thyroid function and 141 (13.4%) with low thyroid function developed MASLD, indicating a statistically significant association (P < 0.05). Univariate regression analysis further revealed that both low thyroid function and subclinical hypothyroidism were significantly associated with MASLD, with hazard ratios of 1.53 (95% CI 1.22–1.92) and 1.95 (95% CI 1.47–2.60), respectively.
In conclusion, the study findings suggest an independent association between MASLD and low thyroid function. This underscores the importance of considering thyroid function in the context of metabolic liver diseases and highlights potential avenues for further research and clinical management strategies.
Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a multifaceted challenge to global public health, with its prevalence reaching alarming levels, affecting nearly a third of the world’s population according to recent meta-analysis findings. This condition, characterized by abnormal fat accumulation in the liver, poses significant health risks, including severe morbidity and mortality. Despite its profound impact, MASLD currently lacks effective pharmacological treatments, leaving liver transplantation as the last resort for patients with advanced MASLD cirrhosis. This underscores the urgent need for novel therapeutic strategies to address this growing health burden.
The etiology and progression of MASLD are intricately intertwined with various metabolic disorders, such as obesity, hypertension, dyslipidemia, and insulin resistance. These metabolic disturbances disrupt the delicate balance of lipid metabolism in the liver, contributing to the development and exacerbation of MASLD. Among the hormones regulating metabolic processes, thyroid hormone holds particular significance. It plays a crucial role in maintaining normal metabolism throughout the body and is instrumental in regulating fat metabolism within the liver.
The thyroid-liver axis serves as a critical nexus in modulating lipid metabolism, where thyroid hormones exert their influence on hepatic lipid accumulation and processing. Hypothyroidism, characterized by insufficient thyroid hormone levels, can disrupt metabolic homeostasis, leading to metabolic disorders and exacerbating liver disease progression. Therefore, understanding the interplay between thyroid function and MASLD is paramount for elucidating the underlying mechanisms and informing therapeutic interventions.
The introduction of the term MASLD in 2023 represented a conceptual shift, replacing the previously used designation of non-alcoholic fatty liver disease (NAFLD). While the differences between these terms may seem subtle, they carry significant implications for the definition, prevalence estimation, and risk factor assessment of the condition. Consequently, it is essential to reassess previous research findings in light of this updated terminology and conceptual framework.
Despite the wealth of research on the relationship between low thyroid function and fatty liver disease, much of the existing literature has focused on NAFLD-defined populations, primarily in Western contexts. This leaves a critical gap in our understanding of how thyroid function influences MASLD specifically and how this relationship may vary across different populations. Given the known racial disparities in metabolic disorders and liver disease prevalence, there is a pressing need to investigate the association between low thyroid function and MASLD in Eastern populations.
Our retrospective cohort study aims to address this knowledge gap by examining the relationship between low thyroid function and MASLD within Eastern populations. By leveraging a diverse demographic cohort, we seek to uncover insights into the nuanced interplay between thyroid function and MASLD across different racial and ethnic groups. Ultimately, our findings aim to inform more tailored and effective approaches to the diagnosis, management, and prevention of MASLD on a global scale.
Method
In a retrospective cohort study spanning from January 2016 to December 2021 at a hospital in Shanghai, China, researchers utilized a database of adult health check-up records. From an initial pool of 3,605 patients, 2901 adults were selected for the study after exclusions based on criteria such as initial fatty liver disease, lack of thyroid function test results, and abnormal thyroid hormone levels.
The study aimed to investigate the association between thyroid function and the incidence of Metabolic Associated Fatty Liver Disease (MASLD). MASLD was defined by ultrasound evidence of hepatic fat accumulation combined with specific cardiometabolic risk factors such as elevated BMI, diabetes, hypertension, and abnormal lipid profile.
Thyroid function categories were defined as follows: strict-normal thyroid function (TSH 0.45–2.5 mIU/L and normal FT4), low thyroid function (TSH ≥ 2.5 mIU/L with normal FT4), low-normal thyroid function (TSH 2.5–4.5 mIU/L with normal FT4), and subclinical hypothyroidism (TSH ≥ 4.5 mIU/L with normal FT4). Thyroid function was assessed using a fully automated chemiluminescent immunoassay analyzer.
Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, while type 2 diabetes mellitus was defined as fasting plasma glucose level ≥6.5 mmol/L.
The study’s findings aimed to contribute to the understanding of the relationship between thyroid function and MASLD incidence, providing valuable insights for clinical management and preventive strategies.
Statistical Analysis
Categorical variables were represented as percentages, while continuous variables were expressed as means along with their respective standard deviations. Comparative analyses between different groups involved Student’s t-test or analysis of variance for continuous variables and the chi-square test for categorical variables. The cumulative incidence of MASLD events was estimated through the Kaplan–Meier method, with group comparisons facilitated by the log-rank test. Univariable and multivariable Cox proportional hazard regression analyses were conducted to explore the association between thyroid function and MASLD development, controlling for potential confounding variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to delineate the risk of MASLD across various thyroid function groups. All reported P values were two-tailed, with statistical significance predetermined at 0.05. The entire statistical analysis was executed using R statistical software version 4.2.1.
Result
In a retrospective cohort study involving 2901 participants without prior Metabolic Associated Fatty Liver Disease (MASLD), significant findings emerged regarding the association between thyroid function and MASLD development. The subjects were categorized into those who developed MASLD (n = 306) and those who did not (n = 2595). Notably, the MASLD group exhibited distinct clinical characteristics compared to the non-MASLD group, including older age, higher prevalence of Type 2 Diabetes Mellitus (T2DM) and hypertension, elevated levels of serum Thyroid-Stimulating Hormone (TSH) and Low-Density Lipoprotein (LDL), higher Body Mass Index (BMI), and glucose levels, alongside lower levels of High-Density Lipoprotein (HDL).
Participants were further stratified based on initial TSH levels into three groups: strict-normal thyroid function, low-normal thyroid function, and subclinical hypothyroidism. During the median follow-up of 15.6 months, statistically significant differences were observed in MASLD incidence among these groups. Specifically, both low thyroid function and subclinical hypothyroidism were found to be significantly associated with MASLD development. This association remained even after adjusting for known risk factors, indicating that low thyroid function independently contributes to MASLD risk. Notably, when low thyroid function was redefined based on TSH levels, subclinical hypothyroidism remained significantly associated with MASLD.
These findings underscore the importance of considering thyroid function as a potential risk factor for MASLD development. Further research and clinical attention in this area may aid in better understanding and managing the complexities of MASLD and its associated risk factors.
Conclusion
The retrospective cohort study revealed a significant association between Metabolic Associated Fatty Liver Disease (MASLD) and low thyroid function, independent of various demographic and metabolic factors. While subclinical hypothyroidism emerged as an independent risk factor for MASLD, there was no notable link detected between low-normal thyroid function and MASLD risk. The study underscores the influence of thyroid hormones on hepatic lipid metabolism and highlights the potential implications for metabolic liver disorders like MASLD.
While previous research has yielded mixed results regarding the association between hypothyroidism and liver conditions, this study contributes novel insights by focusing on MASLD under updated diagnostic criteria. The distinction between MASLD and Non-Alcoholic Fatty Liver Disease (NAFLD) underscores the need for tailored investigations into their respective risk factors and epidemiological characteristics.
MASLD, recognized as a complex condition with diverse systemic manifestations, imposes a substantial health burden globally, necessitating a deeper understanding of its etiology and risk factors. The identification of thyroid function as a potential determinant of MASLD suggests avenues for novel diagnostic, prognostic, and management strategies. However, further research is warranted to elucidate the extent to which thyroid function correlates with MASLD severity.
Despite limitations such as the single-center data source and missing variables like waist circumference and alcohol consumption status, the study’s strengths lie in its cohort design, which enhances causal inference, and the rigorous diagnostic and testing protocols employed.
In summary, the study underscores the association between low thyroid function and MASLD, offering insights into potential avenues for early detection and intervention. These findings may inform the development of targeted therapeutic approaches to mitigate the global burden of MASLD.
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