BACKGROUND: The IL-33/ST2 axis is involved in the pathogenesis of many diseases such as autoimmune diseases, cancer,and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver failure(HBV-ACLF) are lacking. The present study aimed to determine the prognostic role of serum IL-33/soluble ST2(s ST2) in HBV-ACLF.METHODS: Serum levels of IL-33 and sS T2 in healthy controls(HC, n=18), chronic hepatitis B(CHB, n=27) and HBV-ACLF(n=51) patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected. The follow-up of HBV-ACLF patients lasted for 6 months at least.RESULTS: There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1.However, serum s ST2 level differed significantly among the three groups: highest in the HBV-ACLF group, moderate in the CHB group and lowest in the HC group. There was a reverse correlation between serum s ST2 level and the survival of HBV-ACLF patients. The level of serum s ST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF nonsurvivors remained at a high level during the same period. Furthermore, serum sS T2 level was significantly correlated with laboratory parameters and the most updated prognostic scores(CLIF-C OF score, CLIF-C ACLF score and ACLF grades). Thereceiver operating characteristics curves demonstrated that serum sS T2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sS T2 cut-off points for predicting prognosis in HBV-ACLF patients were 76 ng/mL at week 1 or 53 ng/mL at week 4, respectively. HBV-ACLF patients with serum sS T2 level above the cut-off point often had a worse prognosis than those below the cut-off point.CONCLUSION: Serum s ST2 may act as a promising biomarker to assess severity and predict prognosis of patients with HBV-ACLF and help for the early identification and optimal treatment of HBV-ACLF patients at high risk of mortality. However, studies of the IL-33 / ST2 pathway are involved in the pathogenesis of many diseases such as autoimmune diseases, cancer, and heart failure. However, studies of the IL- 33 / ST2 pathway in HBV- related acute-on-chronic liver failure (HBV-ACLF) are lacking. The present study aimed to determine the prognostic role of serum IL-33 / soluble ST2 (s ST2) in HBV-ACLF.METHODS: Serum levels of IL-33 and sS T2 in healthy controls , n = 18), chronic hepatitis B (CHB, n = 27) and HBV-ACLF (n = 51) patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected. The follow-up of HBV-ACLF patients lasted for 6 months at least.RESULTS: There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1.However, serums ST2 level differed significantly among the three groups: highest in the HBV-ACLF group, moderate in the CHB group and lowest in the HC group. There was a reverse correlation between serums ST2 level and the survival of HBV-A CLF patients. The level of serum s ST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, but that in HBV-ACLF nonsurvivors remained at a high level during the same period. was significantly correlated with laboratory parameters and the most updated prognostic scores (CLIF-C OF score, CLIF-C ACLF score and ACLF grades). Thereceiver operating characteristics curves said that serum sS T2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sS T2 cut-off points for predicting prognosis in HBV-ACLF patients were 76 ng / mL at week 1 or 53 ng / mL at week 4, respectively. HBV -ACLF patients with serum sS T2 level above the cut-off point often had a worse prognosis than that below the cut-off point. CONCLUSION: Serum s ST2 may act as a promising biomarker to assess severity and predict prognosis of patients with HBV-ACLF and help for the early identification and optimal treatment of HBV-ACLF patients at high risk of mortality.