Thyroid-Liver Axis: The Role of Thyroid Dysfunction in the Pathogenesis and Progression of MASLD: A Comprehensive...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes of chronic liver disease worldwide with an estimated prevalence ranging between 30% and 38% of the global population. Increasing evidence highlights the complex role of thyroid dysfunction in MASLD pathogenesis. Although many aspects remain unclear, thyroid dysfunction is emerging as a potential risk factor. Thyroid hormones (THs) regulate crucial metabolic processes, including lipid metabolism and mitochondrial function, both central to the development and progression of MASLD. Dysregulated thyroid signalling exacerbates hepatic lipid accumulation, insulin resistance and inflammation, thereby accelerating the progression to more severe stages, such as metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. This review aims to explore in depth the existing relationships between the liver and thyroid, hypothesizing the existence of a thyroid-liver axis. It highlights the biochemical and metabolic connections that influence the onset and progression of MASLD, aiming to summarise current knowledge into a comprehensive overview and emphasise the clinical implications of thyroid function assessment in MASLD patients. Current evidence suggests that approximately one-third of MASLD patients present thyroid dysfunction, underlying the need for systematic thyroid function testing in this population. Moreover, therapies targeting thyroid hormone receptors, particularly THR-β agonists, show promising results in improving hepatic steatosis, inflammation and systemic metabolic parameters. Targeting the thyroid-liver axis through selective THR-β agonists is emerging as a groundbreaking strategy with the potential to reshape the therapeutic landscape of MASLD. Nevertheless, further studies are required to clarify the specific contribution of THR-β in MASLD and to define its potential as a therapeutic target. Integrating personalised and multidisciplinary strategies, including routine thyroid function evaluation and targeted therapeutic interventions, could improve disease management and long-term outcomes in MASLD patients.