Pirfenidone and nintedanib slow functional decline in IPF but do not reverse established fibrosis; Resmetirom is FDA-approved for noncirrhotic MASH with moderate to advanced fibrosis but reverses fibrosis only partially.
Abstract Fibrosis is a maladaptive pathophysiological process characterized by excessive deposition of extracellular matrix resulting from dysregulated tissue repair responses. Fibrosis can affect nearly all organ systems, such as the lung, heart, liver, and kidney. Persistent fibrotic remodeling leads to architectural distortion, loss of function, organ failure, and ultimately increased mortality. These devastating outcomes highlight the urgent need for effective antifibrotic therapies. Advances in multiomics technologies have revealed that fibrosis represents a dynamic alteration spanning the molecular, cellular, microenvironmental, and organ levels. Despite impressive progress in our understanding of fibrogenesis over recent years, a substantial translational gap remains between identifying potential antifibrotic targets and translating this theoretical knowledge into effective human therapies. To further understand pathogenesis and facilitate the development of novel antifibrotic drugs, this review summarizes crucial milestones in fibrosis research, elaborates on organ-specific pathogenic mechanisms, and details the phenotypic and functional changes in critical cellular players, including parenchymal cells, fibroblasts, endothelial cells, and immune cells. Furthermore, this review outlines the key signaling pathways implicated in the pathogenesis of fibrosis, provides a comprehensive overview of relevant clinical trials, and discusses promising future research directions, including cross-organ multiomics integration, chimeric antigen receptor therapy, and artificial intelligence technology applications.
Chen et al. (Fri,) conducted a review in Patients with idiopathic pulmonary fibrosis (IPF) or metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced fibrosis. Pirfenidone and Nintedanib for IPF; Resmetirom and Semaglutide for MASH vs. Placebo or standard of care was evaluated on Slowing disease progression or functional decline in IPF and liver fibrosis in MASH. Pirfenidone and nintedanib slow functional decline in IPF but do not reverse established fibrosis; Resmetirom is FDA-approved for noncirrhotic MASH with moderate to advanced fibrosis but reverses fibrosis only partially.