Liver, Portal, and Systemic Thyroid Hormone Concentrations in End-Stage MASH Reveal Distinct Roles for T3/rT3 Ratio...

Area of Science:

• Endocrinology
• Hepatology
• Metabolic Disorders

Background:

• The liver plays a crucial role in thyroid hormone (TH) metabolism, converting thyroxine (T4) to triiodothyronine (T3) and clearing reverse T3 (rT3).
• Selective thyromimetics targeting the TH receptor β are emerging treatments for metabolic dysfunction-associated steatohepatitis (MASH).
• Understanding TH metabolism alterations in MASH patients is essential for developing targeted therapies.

Purpose of the Study:

• To investigate specific changes in TH concentrations within the liver and circulation of patients with end-stage MASH.
• To characterize TH metabolism in human MASH and identify potential biomarkers for diagnosis and prognosis.

Main Methods:

• A cross-sectional study involving 12 patients with MASH cirrhosis and 12 healthy controls.
• Intraoperative collection of liver tissue, portal plasma, and systemic plasma.
• Quantification of total T4, T3, and rT3 using liquid chromatography-tandem mass spectrometry.

Main Results:

• MASH cirrhosis patients showed lower T3 and T4 levels and elevated rT3 in all measured compartments.
• The T3/rT3 ratio, an indicator of deiodinase activity, was significantly suppressed in MASH patients.
• Hepatic T3 and the systemic T3/rT3 ratio effectively discriminated MASH from healthy controls.
• Systemic T4 levels correlated inversely with MELD and Child-Pugh scores, indicating disease severity.

Conclusions:

• This study provides direct evidence of intrahepatic hypothyroidism in human end-stage MASH.
• Hepatic T3 and the systemic T3/rT3 ratio serve as potent biomarkers for MASH diagnosis.
• Systemic T4 concentration is a valuable indicator of disease severity in MASH cirrhosis.