Abstract

Background and 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 (χ2 = 24.69, P < 0.01) and HCs (χ2 = 35.93, P < 0.01). Meanwhile, TACE methylation was significantly lower in CHB patients than HCs (χ2 = 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).

Conclusion
This study showed that demethylation of TACE promoter occurred in ACHBLF and might serve as a potential prognostic marker.