Therapeutic HNF4A mRNA attenuates liver fibrosis in a preclinical model

•Restoration of HNF4A via mRNA delivery improves functions of fibrotic primary hepatocytes from both mice and humans.•The mRNA encapsulated in lipid nanoparticles can be delivered into hepatocytes of the fibrotic liver.•Lipid nanoparticle-mediated HNF4A mRNA delivery ameliorates fibrosis and cirrhosis in different chronic liver injury models.•Paraoxonase 1, a therapeutic target of HNF4A, contributes to anti-fibrotic effects of HNF4A.•HNF4A mRNA delivery affects macrophage infiltration and polarization as well as hepatic stellate cell activation.