Demethylation of tumor necrosis factor a converting enzyme predicts poor prognosis in acute on chronic hepatitis B liver failure.
BACKGROUND AND OBJECTIVE Tumor necrosis factor a 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 a, sTNFRI, sTNFRII were measured by enzyme linked immunosorbent assay. RESULTS TACE methylation was significantly lower in patients with ACHBLF than those with CHB (kh(2)=24.69, P<0.01) and HCs (kh(2)=35.93, P<0.01) Meanwhile, TACE methylation was significantly lower in CHB patients than HCs (kh(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 a, 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) CONCLUSION This study showed that demethylation of TACE promoter occurred in ACHBLF and might serve as a potential prognostic marker.
Clinics and research in hepatology and gastroenterology