Thus, HMGB1 may be synergistically released by the above two pathways as a result of infection and cell damage, leading to exacerbated inflammation and injury of the bile duct, particularly the newly formed cholangioles, intrahepatic cholestasis, and hyperbilirubinemia during the process of ACLF. The gene discussed is HMGB1; the disease is intrahepatic cholestasis.