Thyroid-Liver Axis: Mechanistic Insights and Clinical Implications.

Area of Science:

• Endocrinology
• Hepatology
• Metabolic Diseases

Background:

• The thyroid and liver have a crucial bidirectional relationship impacting metabolic regulation and hormonal balance.
• Thyroid hormones (THs) influence liver functions like lipid handling and glucose metabolism, while the liver affects TH transport and metabolism.
• Thyroid dysfunction is increasingly linked to metabolic dysfunction-associated steatotic liver disease (MASLD), fibrosis, and poor metabolic health.

Purpose of the Study:

• To synthesize current knowledge on thyroid-liver interactions, focusing on mechanistic, clinical, and therapeutic aspects.
• To explore the implications of these interactions for clinical practice and patient management.
• To review emerging thyroid hormone-based therapies for liver diseases.

Main Methods:

• A comprehensive narrative review of mechanistic, clinical, and translational studies.
• Inclusion of studies on thyroid dysfunction, liver disease, thyroid hormone sensitivity, and novel therapies.
• Focus on evidence related to metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH).

Main Results:

• Thyroid dysfunction exacerbates MASLD, dyslipidemia, insulin resistance, and liver injury.
• Liver disease alters thyroid hormone metabolism, complicating thyroid function test interpretation (e.g., nonthyroidal illness syndrome).
• Reduced intrahepatic thyroid hormone signaling and tissue sensitivity are implicated in steatosis and fibrosis progression.

Conclusions:

• Understanding thyroid-liver interactions improves the interpretation of thyroid abnormalities in liver disease and aids risk stratification for metabolic liver disorders.
• Liver-targeted thyroid hormone receptor-β agonists, like resmetirom, offer a significant therapeutic advance for metabolic dysfunction-associated steatohepatitis (MASH).
• Further research is needed on diagnostic indices, long-term safety of thyromimetics, and the role of thyroid hormone replacement in liver therapy.