AIM: To evaluate tumor necrosis factor-α convertingenzyme (TACE) methylation status in patients withchronic hepatitis B (CHB).METHODS: Eighty patients with hepatitis B e antigen(HBeAg)-positive CHB, 80 with HBeAg-negative CHB,and 40 healthy controls (HCs) were randomly enrolled inthis study. Genomic DNA was extracted from peripheralblood mononuclear cells and methylation status ofTACE promoter was determined by methylation-specificpolymerase chain reaction. The clinical and laboratoryparameters were collected.RESULTS: One hundred and thirty of 160 patients withCHB (81.25%) and 38 of 40 HCs (95%) displayed TACEpromoter methylation. The difference was significant (χ^2 = 4.501, P 〈 0.05). TACE promoter methylationfrequency in HBeAg-positive CHB (58/80, 72.5%) wassignificantly lower than that in HBeAg-negative CHB(72/80, 90%; χ^2 = 8.041, P 〈 0.01) and HCs (χ^2 =8.438, P 〈 0.01). However, no significant difference wasobserved in the methylation frequency between HBeAgnegativeCHB and HCs (χ ^2 = 0.873, P 〉 0.05). In theHBeAg-positive group, TACE methylation frequencywas significantly negatively correlated with HBeAg (r =-0.602, P 〈 0.01), alanine aminotransferase (r = -0.461,P 〈 0.01) and aspartate aminotransferase (r = -0.329,P 〈 0.01).CONCLUSION: Patients with HBeAg-positive CHBhave aberrant demethylation of the TACE promoter,which may potentially serve as a biomarker for HBeAgseroconversion.