Based on the close relationship between HMGB1 and TGF-β1 and the PI3K/AKT pathway in various fibrotic diseases, the HMGB1/TGF-β1 and HMGB1/RAGE/PI3K/AKT pathways may have a synergistic effect in granuloma-associated liver fibrosis, although little has been reported about any direct connections, such as whether upregulation of the TGF-β1/Smad pathway is mediated by the RAGE binding site of HMGB1. This evidence concerns the gene HMGB1 and Granuloma.