ABSTRACT:In this study ,we elucidated the predictors of progression to liver failure during severe acute exacerbation .We analyzed 69 consecutive patients with severe acute exacerbation of chronic hepatitis B for clinical outcome and factors that influ‐enced the development of liver failure ,including viral genotype ,PC (G1896A) and BCP (A1762T/G1764A) mutants .Thirty‐three (47 .8% ) severe acute exacerbation patients progressed to liver failure .Multivariate analysis identified serum bilirubin (TB>256 μmol/dL ,P=0 .008) and prothrombin activity (PTA<40% ,P<0 .001) as significant determinants of progression to liver failure .HBeAg negativity (P=0 .065) and PC mutant (P=0 .090) were associated with the progression to hepatic de‐compensation .Serum total bilirubin ,prothrombin activities ,HBeAg status and PC mutant were predictors of clinical outcome in patients with severe acute exacerbation of chronic hepatitis B .