title: Aberrant GSTP1 promoter methylation predicts short-term prognosis in acute-on-chronic hepatitis B liver failure.
abstract: BACKGROUND
  Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF).
  
  
  OBJECTIVE
  To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis.
  
  
  METHODS
  One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained.
  
  
  RESULTS
  GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-on-chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut-off points showed significantly poorer survival than those below (P < 0.05).
  
  
  CONCLUSIONS
  Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: S
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: F-K
authors.initials: FK
authors.lastname: Sun
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.|Institute of Hepatology, Shandong University, Jinan, China.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Fan
authors.affiliation: Department of Hepatology, Qingdao Infectious Disease Hospital, Qingdao, China.
authors.forename: C-H
authors.initials: CH
authors.lastname: Shi
authors.affiliation: Department of Hepatology, Jinan Infectious Disease Hospital, Jinan, China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: L-Y
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.|Institute of Hepatology, Shandong University, Jinan, China.
authors.forename: K
authors.initials: K
authors.lastname: Wang
mesh_terms: D000328:Adult; D001663:Bilirubin / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D017093:Liver Failure / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D005982:Glutathione Transferase; D001663:Bilirubin