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Background and aimsFew drugs have been confirmed to be effective for fulminant hepatic failure (FHF). The purpose of this study was to prepare sterically stable liposomes (SSL) encapsulating hepatic stimulator substance (HSS) and determine their therapeutic effect on FHF.HSS were encapsulated into SSL (HSS-SSL). FHF was induced in rats by thioacetamide (TAA) injection (400 mg/kg, three times with a 24-h interval). The agents, including HSS-SSL, SSL, HSS, and sodium chloride (NS), were each injected intravenously 2 h after the second and the third TAA injection.Freshly prepared HSS-SSL had a mean size of 93.59 nm and the average encapsulation efficiency was 37.20%. HSS encapsulated in SSL showed a longer half life and more potent target to injured livers than free HSS. Twenty-four hours after the third TAA-injection, the survival rate of HSS-SSL-treated rats (80%) was significantly higher than that of rats treated with NS (20%), SSL (25%), or HSS (50%). Histopathologic examination showed that there was the least necrosis and inflammation in the livers of HSS-SSL-treated rats. The incidence of stage 3 or 4 hepatic encephalopathy in HSS-SSL-treated rats was significantly lower than that in rats treated with other agents. The serum pro-inflammatory cytokine levels and hepatic lipid peroxidation levels were both markedly reduced, while hepatocyte proliferative rate was markedly increased after HSS-SSL treatment.Encapsulation by SSL markedly improved the therapeutic effect of HSS on FHF in rats. Encapsulation by SSL may be an effective approach to enhance the therapeutic potency of drugs for FHF.