Dear Editor,
We read with interest the study by Jin et al. [
1], as it sheds light on the significant association between hypothyroidism and the progression of metabolic dysfunction-associated steatohepatitis (MASH) and its impact on liver-related events (LREs). Their findings indicate that both subclinical and overt hypothyroidism are significantly associated with an increased risk of LREs in patients with MASH [
1]. These findings underscore the critical importance of recognizing individual metabolic risk factors, such as hypothyroidism, and highlight the necessity of a holistic approach to metabolic health.
With global lifestyle changes contributing to the rise of obesity, affecting over 1.9 billion people worldwide, and physical inactivity impacting more than 27% of the global population, the prevalence of metabolic diseases, including diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD), is increasing [
2]. Understanding the core pathways connecting these conditions, such as the deterioration of metabolic health, systemic meta-inflammation, and gut microbiome alterations, has led to increasing efforts to reshape our approach to clinical care, research, and drug development, moving from a single disease to a more comprehensive framework that considers these conditions collectively, while also recognizing the differences and specificities that may exist. The unprecedented success of glucagon-like peptide-1 in treating various metabolic diseases exemplifies this approach, and other treatment candidates with similar broad effects will likely emerge [
3].
In this context, the American Heart Association (AHA) recently introduced the concept of cardiovascular-kidney-metabolic syndrome to highlight the intricate link between cardiovascular, renal, and metabolic dysfunctions [
4]. Notably, the liver was not included in this framework, despite its central role in regulating systemic metabolic health. Robust evidence indicates that the presence of metabolic dysfunction-associated fatty liver disease/metabolic dysfunction-associated steatotic liver disease (MAFLD/MASLD) is a strong risk factor for metabolic health deterioration in individuals classified as metabolically healthy obese (MHO). Moreover, individuals with MHO and MAFLD/MASLD exhibit an elevated 10-year cardiovascular risk and a threefold increased risk of developing diabetes compared to those with MHO who do not have MAFLD/MASLD. Steatosis could serve as an early indicator of metabolic health deterioration prior to the overt emergence of other conditions, such as hypertension, CKD, and CVD [
5]. In 2025, the American Diabetes Association (ADA) recommends that MAFLD/MASLD should be routinely assessed and managed in patients with diabetes, suggesting some progress in recognising that liver disease is not merely a secondary condition but a clinically relevant metabolic comorbidity that warrants integration into contemporary metabolic health frameworks [
6].
One of the key motivations behind the redefinition of fatty liver disease in recent years has been to better recognize the role of metabolic dysfunction in its development, aligning it more closely with other metabolic diseases [
2]. The aforementioned aspects emphasize that although some progress has been made, there is still a need for a more coordinated effort within the hepatology community to enhance awareness of the liver’s role in overall metabolic health. To achieve this, some practical steps include: efforts for harmonisation of nomenclature and definition of fatty liver disease, Launching targeted awareness campaigns to increase healthcare professionals’ understanding of liver health and advocating for the liver’s central role in metabolic health, Integrating a multidisciplinary care team approach, advocating for integration of liver health education into general wellness programs and public health initiatives and engaging the media to cover stories about MAFLD/MASLD. This recognition is crucial for developing comprehensive healthcare policies, advancing research, and facilitating drug development, ultimately aiming to provide the best care for patients by addressing all of their active diseases and improving the shared underlying metabolic dysfunction.
FOOTNOTES
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Authors’ contribution
Shadi Zerehpoosh: Investigation, writing - original draft, writing - review and editing. Ziyan Pan: Writing - review and editing. Mohammed Eslam: Investigation, writing - review and editing.
-
Acknowledgements
Mohammed Eslam is supported by a National Health and Medical Research Council of Australia (NHMRC) investigator and ideas grants (AAP2008983 and APP2001692).
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Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
American Diabetes Association
American Heart Association
metabolic dysfunction-associated fatty liver disease/metabolic dysfunction-associated steatotic liver disease
metabolic dysfunction-associated steatohepatitis
metabolically healthy obese
REFERENCES
- 1. Jin X, Song SJ, Lai JC, Wong GL, Kong AP, Peng N, et al. Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol 2026;32:353-367.
- 2. Eslam M, Ahmed A, Després JP, Jha V, Halford JCG, Chieh JTW, et al. Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases. Lancet Gastroenterol Hepatol 2021;6:743-753.
- 3. Eslam M, Fan JG, Yu ML, Wong VW, Cua IH, Liu CJ, et al. The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease. Hepatol Int 2025;19:261-301.
- 4. Ndumele CE, Rangaswami J, Chow SL, Neeland IJ, Tuttle KR, Khan SS, et al. Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association. Circulation 2023;148:1606-1635 Erratum in: Circulation 2024;149:e1023.
- 5. Kouvari M, Chrysohoou C, Skoumas J, Pitsavos C, Panagiotakos DB, Mantzoros CS, et al. The presence of NAFLD influences the transition of metabolically healthy to metabolically unhealthy obesity and the ten-year cardiovascular disease risk: a population-based cohort study. Metabolism 2022;128:154893.
- 6. American Diabetes Association Professional Practice Committee. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of care in diabetes-2025. Diabetes Care 2025;48 Suppl 1:S59-S85.
Citations
Citations to this article as recorded by
- Reply to correspondence on “Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease”
Shadi Zerehpoosh, Ziyan Pan, Mohammed Eslam
Clinical and Molecular Hepatology.2026; 32(3): e450. CrossRef - Correspondence to letter to the editor on “Hypothyroidism and the risk of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease”
Xinrui Jin, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
Clinical and Molecular Hepatology.2026; 32(3): e422. CrossRef
