The thyroid hormone receptor beta (THR-β) agonist resmetir for the treatment of liver fi brosis and steatohepatitis

Subclinical elevations in thyroid-stimulating hormone (TSH) levels, a key indicator of thyroid dysfunction, positively correlate with biochemical markers of hepatocellular damage. The thyroid hormones triiodothyronine (T3) and thyroxine (T4) act as fundamental biochemical regulators, determining metabolic homeostasis in both hepatocytes and the body as a whole. An innovative class of drugs, THR-β agonists, target hepatocytes by selectively activating the THR-β receptor isoform, which is expressed primarily in the liver and regulates a number of metabolic processes. The high short-term efficacy and safety confirmed in the MAESTRO-NASH study have led to the consideration of resmetirom (and the THR-β agonist class as a whole) as a promising new treatment option for ASH and liver fibrosis. The antifibrotic potential of resmetirom was confirmed by the results of improvement in fibrosis stage ≥1 without worsening NAFLD activity in 24.2% of those receiving 80 mg and in 25.9% of those receiving 100 mg, versus 14.2% on placebo. A positive effect of therapy on key biochemical markers was revealed. Along with a significant decrease in the activity of liver enzymes (ALT, AST, GGT), a pronounced lipid-lowering effect on LDL was recorded: a decrease of 13.6% (80 mg) and 16.3% (100 mg) by week 24 versus a minimal change in the placebo group (+0.1%, p