title: Serum soluble ST2 is a promising prognostic biomarker in HBV-related acute-on-chronic liver failure.
abstract: 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 (sST2) in HBV-ACLF.
  
  
  METHODS
  Serum levels of IL-33 and sST2 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 sST2 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 sST2 level and the survival of HBV-ACLF patients. The level of serum sST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF non-survivors remained at a high level during the same period. Furthermore, serum sST2 level was significantly correlated with laboratory parameters and the most updated prognostic scores (CLIF-C OF score, CLIF-C ACLF score and ACLF grades). The receiver operating characteristics curves demonstrated that serum sST2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sST2 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 sST2 level above the cut-off point often had a worse prognosis than those below the cut-off point.
  
  
  CONCLUSIONS
  Serum sST2 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.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. xieqingrjh@163.com.
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Jiang
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Xiang
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Mo
authors.forename: Lan-Yi
authors.initials: LY
authors.lastname: Lin
authors.forename: Shi-San
authors.initials: SS
authors.lastname: Bao
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000821:virology; D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006509:Hepatitis B / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood*; D000067596:Interleukin-33 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33