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

The study by Dr. Manka and colleagues explores the role of thyroid hormones (THs) in nonalcoholic steatohepatitis (NASH) and liver fibrosis, focusing on cell type-specific actions. They found that THs regulate hepatic stellate cells (HSCs) via thyroid hormone receptor (TR)α and transforming growth factor (TGF)β signaling. Experimental deletion of TRα in mice increased liver fibrosis, while pharmacologic TR agonism reduced fibrogenic responses. The study suggests that targeting TRα in HSCs could be a potential therapeutic strategy for liver fibrosis. However, systemic TH replacement therapy is not viable due to adverse effects, highlighting the need for liver-directed treatments. The findings emphasize the importance of local TH actions in liver cells and suggest future research directions for developing cell type-specific therapies.