Study Uncovers Potential New Drug Targets for Liver Fibrosis

Using RNA sequencing and other technologies, a team led by scientists from Icahn School of Medicine at Mount Sinai has identified several potential new therapeutic targets for liver fibrosis. The prevalence of non-alcoholic fatty liver disease is rapidly increasing globally, with a large number of patients progressing to a more advanced stage of the disease — called nonalcoholic steatohepatitis (NASH) and for which there are no approved therapies — involving the activation of hepatic stellate cells (HSCs) to drive hepatic fibrosis. The researchers used single-nucleus RNA-seq and advanced 3D imaging to profile gene expression changes in in HSCs from both human and murine NASH, uncovering a profibrotic autocrine signaling loop comprising dozens of receptor-ligand pairs that emerges in hepatic stellate cells specifically during late-stage disease. As reported in Science Translational Medicine this week, they show that inhibiting one of these receptor-ligand interactions pharmacologically could reduce advanced fibrosis in a mouse model of NASH. "The findings suggest a therapeutic paradigm in which stage-specific therapies could yield enhanced antifibrotic efficacy in patients with advanced hepatic fibrosis," the study's authors write