Objective To investigate the short- term prognosis in hepatitis B virus (HBV) - related acute- on- chronic liver failure (ACLF) treated with artificial liver support system (ALSS) and its relationship with clinical indices including HBeAg and to provide reference for the timely, accurate prognostic evaluation of HBV- related ACLF.Methods A retrospective analysis was performed on the clinical data of 81 patients with HBV- related ACLF (55 HBeAg- negative cases and 26 HBeAg- positive cases) who received ALSS treatment and comprehensive medical treatment.The HBeAg- negative cases and HBeAg- positive cases were compared in terms of treatment outcome and laboratory indices including alanine aminotransferase, total bilirubin, albumin, prealbumin (PA) , cholinesterase, international normalized ratio (INR) , blood ammonia, and alpha- fetoprotein (AFP) .Comparison between two groups was made by chi- square test or non- parametric test.Results There was no significant difference in treatment outcome between the HBeAg- negative cases and HBeAg- positive cases (P = 0.158) .There were significant differences in PA, AFP, and INR between the patients with response to treatment and those without response to treatment (P < 0.000 1, P = 0.000 5, and P < 0.000 1) .The receiver operating characteristic (ROC) curves of PA, AFP, and INR were drawn, and their areas under the ROC curves were 0.875, 0.795, and 0.792, respectively.Conclusion There is no significant difference in treatment outcome between HBeAg- positive and HBeAg- negative patients with HBV- related ACLF treated with ALSS.PA, AFP, and INR can be used as accurate indices for prognostic evaluation of HBV- related ACLF.