Therapeutic targeting of liver progenitor cells in chronic liver disease via PRI-724 inhibition of the Wnt/beta-catenin pathway

Background and Aim: Hepatocellular carcinoma (HCC) accounts for 85–90% of primary liver cancers and is associated with poor patient outcomes. Metabolic‐associated fatty liver disease (MAFLD), a major risk factor for HCC, has become the most common chronic liver disease, and there are no pharmacological treatments available. A prominent feature of all chronic liver diseases is the proliferation of liver progenitor cells (LPCs). Their numbers are directly proportional to the underlying disease severity and significantly correlate with the degree of inflammation and fibrosis, which has suggested LPCs as a potential therapeutic target. We aimed to investigate the expression and pharmacological inhibition of Wnt/beta‐catenin signaling in an in vitro model of fat‐loaded LPCs and a mouse model of MAFLD, which features steatosis, inflammation, fibrosis, and LPC proliferation..