Objective To investigate the effects of antiviral drugs,lamivudine(LAM) and entecavir(ETV),on the short-term outcome in patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).Methods The demographic and clinical data of 445 patients with HBV-related ACLF(LAM∶ ETV,333∶ 112) who were hospitalized in the First Clinical Medical College of Fujian Medical University from January 2004 to December 2010 were collected,including age,sex,complications,clinical biochemical parameters,coagulation parameters,the use of antiviral drug,artificial liver treatment,and the survival at 24 weeks.The independent risk factors for the outcome at 24 weeks were determined by univariate and multivariate logistic regression analyses.Results The univariate analysis indicated that the LAM group had significantly higher globulin,total bilirubin(TBil),alanine aminotransferase,international normalized ratio(INR),serum creatinine,and model for end-stage liver disease(MELD) score than the ETV group(P < 0.05),but had significantly lower cholinesterase and prothrombin time activity(PTA) than the ETV group(P < 0.05).The death group had significantly older age,higher incidence rates of liver cirrhosis,hepatic encephalopathy,spontaneous bacterial peritonitis,pulmonary infection,mycotic infection,electrolyte disturbance,hepatorenal syndrome,and upper gastrointestinal hemorrhage,and higher TBil,INR,white blood count,and MELD score than the survival group(P < 0.05),but had significantly lower albumin,gamma-glutamyl transpeptidase,cholesterol,cholinesterase,serum sodium,PTA,alpha-fetoprotein,hemoglobin,platelet,and positive rate of HBe Ag than the survival group(P < 0.05).And there was no significant difference in the use of antiviral drugs(LAM∶ ETV) between the death group and the survival group(P = 0.21).The multivariate logistic regression analysis showed that older age,hepatic encephalopathy,hepatorenal syndrome,lower cholinesterase,lower PTA,and higher DBil were the independent risk factors for overall mortality at 24 weeks,and the artificial liver treatment was a protective factor.Conclusion The selection of antiviral drugs(LAM and ETV) does not affect the short-term outcome in patients with HBV-related ACLF.The age,hepatic encephalopathy,hepatorenal syndrome,lower cholinesterase,lower PTA,and higher DBil are the independent risk factors for the short-term outcome,and the artificial liver treatment is a protective factor.