Cell Type-Specific Actions of Thyroid Hormones in Nonalcoholic Steatohepatitis and Liver Fibrosis

The study by Dr. Manka and colleagues investigates the role of thyroid hormones (THs) in nonalcoholic steatohepatitis (NASH) and liver fibrosis, emphasizing cell type-specific actions. They discovered that THs influence hepatic stellate cells (HSCs) through thyroid hormone receptor alpha (TRα) and transforming growth factor beta (TGFβ) signaling. Deleting TRα in mice led to increased liver fibrosis, while activating TRα pharmacologically reduced fibrogenic responses. The findings suggest that targeting TRα in HSCs could be a promising therapeutic approach for liver fibrosis, though systemic TH replacement therapy is not feasible due to adverse effects. Future research should aim at cell type-specific or liver-directed therapies to locally modulate TH metabolism.