title: High promoter methylation levels of glutathione-S-transferase M3 predict poor prognosis of acute-on-chronic hepatitis B liver failure.
abstract: OBJECTIVE
  This study aimed to evaluate the prognostic value of glutathione-S-transferase M3 (GSTM3) gene promoter methylation in patients with acute-on-chronic hepatitis B liver failure (ACHBLF).
  
  
  METHODS
  A total of 119 patients with ACHBLF, 60 patients with chronic hepatitis B and 30 healthy controls were enrolled. We used a quantitative methylation detection technique, MethyLight, to examine the methylation levels of GSTM3 in peripheral blood mononuclear cells.
  
  
  RESULTS
  The GSTM3 methylation level was significantly higher in patients with ACHBLF than those in patients with chronic hepatitis B and healthy controls (both P < 0.05). In patients with ACHBLF, GSTM3 methylation level percentage of methylated reference (PMR) positively correlated with total bilirubin, international normalized ratio, and Model for End-stage Liver Disease (MELD) score, and negatively correlated with prothrombin activity and albumin (all P < 0.05). The PMR for GSTM3 of non-survivors was significantly increased compared to that of survivors (P < 0.05). Multivariate analysis indicated that GSTM3 methylation level was one of the independent prognostic factors for 3-month mortality of ACHBLF (P = 0.000). The area under the receiver-operator characteristic curve of PMR for GSTM3 in predicting 3-month mortality of ACHBLF was not statistically different from that of MELD score (0.798 vs. 0.716, P = 0.152). However, the area under the curve of PMR for GSTM3 was significantly higher than that of MELD score in predicting 1-month mortality (0.887 vs. 0.737, P = 0.020).
  
  
  CONCLUSIONS
  Promoter methylation levels of GSTM3 in peripheral blood mononuclear cells closely correlated with disease severity and could be used to predict prognosis of patients with ACHBLF.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Feng-Kai
authors.initials: FK
authors.lastname: Sun
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.|Institute of Hepatology, Shandong University, Jinan, China.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.affiliation: Department of Hepatology, Qingdao Infectious Disease Hospital, Qingdao, China.
authors.forename: Chang-He
authors.initials: CH
authors.lastname: Shi
authors.affiliation: Department of Hepatology, Jinan Infectious Disease Hospital, Shandong University, Jinan, China.
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Xin-You
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Xiang-Fen
authors.initials: XF
authors.lastname: Ji
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.|Institute of Hepatology, Shandong University, Jinan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
keywords: acute-on-chronic hepatitis B liver failure; methylation; prognosis; quantitative