摘要Background:It has been demonstrated that thymosin β 4(T β 4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine T β 4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).T β 4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of T β 4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of T β 4 mRNA showed the opposite trend.In patients with ACHBLF,T β 4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,T β 4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,T β 4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of T β 4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:T β 4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.