In conclusion, through in vivo and in vitro experiments, a combination of NEP-i and ARB effectively prevents the progression of murine liver fibrosis and this effect is associated with the inhibition of HSC proliferation and pro-fibrogenic activity by activating ANP-dependent GC-A/cGMP/PKG signaling and inhibiting AT-II-dependent AT1R/PKC signaling. This evidence concerns the gene NPPA and Hepatic fibrosis.