Hepatic fibrosis is a key pathological stage where chronic liver disease often progresses to more serious conditions like cirrhosis and liver cancer. It is commonly caused by factors such as viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. At present, there are no specific drugs available to effectively treat fibrosis. The transforming growth factor-β (TGF-β) signaling pathway plays a central role in this process—mainly by activating hepatic stellate cells, promoting the buildup of extracellular matrix, and regulating the immune microenvironment. Due to its important function, this pathway has become a promising target for new treatments. This review systematically summarizes the research status of TGF-β signaling pathway inhibitors, including small-molecule kinase inhibitors, soluble receptors, monoclonal antibodies, natural products, and traditional Chinese medicine formulas. Studies have shown that these inhibitors produce notable anti-fibrotic effects in laboratory settings and in different animal models. The aim of this review is to provide an overview of existing findings and to offer insights for future liver fibrosis targeted therapies, which may involve personalized medicine and combination strategies.

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