Thyroid function, adipokines and mitokines in metabolic dysfunction-associated steatohepatitis: A multi-centre...

Area of Science:

• Hepatology
• Endocrinology
• Metabolic Diseases

Background:

• The thyroid axis is being investigated as a potential therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD).
• Thyroid function was evaluated across the full spectrum of MASLD.
• Understanding thyroid function's role is crucial for developing targeted MASLD therapies.

Purpose of the Study:

• To examine thyroid function in patients with MASLD.
• To determine the association between thyroid-stimulating hormone (TSH) levels and liver disease severity, including fibrosis and metabolic dysfunction-associated steatohepatitis (MASH).
• To explore the potential of thyroid hormone modulation as a therapeutic strategy for MASLD.

Main Methods:

• Recruited 677 subjects with MASLD, excluding those with abnormal free thyroxine.
• Classified participants based on standard thyroid-stimulating hormone (TSH) criteria: subclinical hyperthyroidism, euthyroidism (low/high TSH), and subclinical hypothyroidism.
• Analyzed associations between TSH levels and liver outcomes, controlling for metabolic factors.

Main Results:

• Elevated TSH levels correlated with significant fibrosis (F≥2), MASH, and at-risk MASH.
• Subclinical hypothyroidism showed a significant association with fibrosis (OR=3.47), MASH (OR=3.44), and at-risk MASH (OR=3.88), independent of obesity and insulin resistance.
• Sex-specific analysis indicated a strong link between TSH and fibrosis in women, which was attenuated by adipokine/mitokine adjustment.

Conclusions:

• Findings support investigating thyroid hormone administration for subclinical hypothyroidism in MASLD.
• Suggests exploring liver-specific thyroid receptor agonists for patients across the TSH spectrum in MASLD.
• Highlights the potential therapeutic role of targeting the thyroid axis in MASLD management.