title: Demethylation of tumor necrosis factor-α converting enzyme predicts poor prognosis in acute-on-chronic hepatitis B liver failure.
abstract: OBJECTIVE
  Tumor necrosis factor-α converting enzyme (TACE) has been demonstrated to be involved in liver inflammation. However, the significance of TACE methylation in acute-on-chronic hepatitis B liver failure (ACHBLF) has not been demonstrated. This study aims to evaluate TACE methylation status in ACHBLF and determine its predictive value for prognosis.
  
  
  METHODS
  Forty-five patients with ACHBLF, 80 with chronic hepatitis B (CHB) and 54 healthy controls (HCs) were enrolled. The methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The TACE mRNA expression was determined by quantitative real-time polymerase chain reaction. The plasma levels of TACE, TNF-α, sTNFRI, sTNFRII were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  TACE methylation was significantly lower in patients with ACHBLF than those with CHB (χ(2)=24.69, P<0.01) and HCs (χ(2)=35.93, P<0.01). Meanwhile, TACE methylation was significantly lower in CHB patients than HCs (χ(2)=4.03, P<0.05). TACE methylation was significantly inversely associated with its mRNA expression (r=-0.68; P<0.01). The plasma levels of TACE, TNF-α, sTNFRI, sTNFRII were significantly higher in patients with ACHBLF than those with CHB (P<0.05, respectively) and HCs (P<0.05, respectively). In patients with ACHBLF, significantly higher prothrombin activity, lower total bilirubin and MELD score were found in TACE methylated group than unmethylated group (P<0.05). ACHBLF patients with methylated TACE showed significantly better survival than those without (P<0.01).
  
  
  CONCLUSIONS
  This study showed that demethylation of TACE promoter occurred in ACHBLF and might serve as a potential prognostic marker.
authors: Department of Hepatology, Qilu Hospital of Shandong University, Institute of Shandong University, Wenhuaxi Road 107#, Shandong, Jinan 250012, China.
authors: Zhen-Li
authors: ZL
authors: Wang
authors: Department of Hepatology, Qilu Hospital of Shandong University, Institute of Shandong University, Wenhuaxi Road 107#, Shandong, Jinan 250012, China.
authors: Shuai
authors: S
authors: Gao
authors: Department of Infectious Diseases, Qingdao Women and Children Hospital, Qingdao 266034 Shandong, China.
authors: Lei
authors: L
authors: Li
authors: Department of Hepatology, Qilu Hospital of Shandong University, Institute of Shandong University, Wenhuaxi Road 107#, Shandong, Jinan 250012, China.
authors: Xin-You
authors: XY
authors: Li
authors: Department of Hepatology, Qilu Hospital of Shandong University, Institute of Shandong University, Wenhuaxi Road 107#, Shandong, Jinan 250012, China.
authors: Shu-Ling
authors: SL
authors: Huan
authors: Department of Hepatology, Qilu Hospital of Shandong University, Institute of Shandong University, Wenhuaxi Road 107#, Shandong, Jinan 250012, China; Institute of Hepatology, Shandong University, 250012 Shandong, Jinan, China. Electronic address: wangdoc876@126.com.
authors: Kai
authors: K
authors: Wang
mesh_terms: D000072198:ADAM17 Protein / Q000235:genetics*; D065290:Acute-On-Chronic Liver Failure / Q000401:mortality* / Q000821:virology*; D000328:Adult; D001663:Bilirubin / Q000032:analysis; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011516:Prothrombin / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D011516:Prothrombin; D000072198:ADAM17 Protein; D001663:Bilirubin