Correlation between promoter methylation of glutathione‐S‐tranferase P1 and oxidative stress in acute‐on‐chronic hepatitis B liver failure

Abstract

Promoter methylation of glutathione-S-transferase P1 (GSTP1) may be involved in liver damage caused by oxidative stress in acute-on-chronic hepatitis B-induced liver failure (ACHBLF). This study aimed to explore GSTP1 promoter methylation status and oxidative stress in such patients. DNA was extracted from peripheral blood mononuclear cells (PBMCs) of patients with acute-on-chronic liver hepatitis B-induced liver failure, chronic hepatitis B (CHB) and normal controls, followed by sodium-bisulfite treatment and methylation-specific PCR (MSP) analysis. Plasma malondialdehyde (MDA) adducts levels were detected by enzyme-linked immunosorbent assay as oxidative stress marker. Model for end-stage liver disease (MELD) score was employed to estimate the severity of the liver failure. Eleven of 35 patients with acute-on-chronic liver failure and 3 of 35 patients with stab le hepatitis B displayed GSTP1 promoter methylation, and the difference was significant (χ2) = 5.71, P = 0.02). No differences in standard liver function tests were found in patients with acute-on-chronic liver failure with and without GSTP1 promoter methylation although the levels of total bilirubin were greater in those with methylation. The levels of MDA adducts were significantly higher in patients with liver failure when compared to those with CHB (12.44 ± 5.38 pmol/mg vs 8.42 ± 5.49 pmol/mg, P < 0.01), and in the patients with liver failure who had promoter methylation the levels were higher than in those who did not (15.2 ± 4.68 pmol/mg vs 11.17 ± 5.29 pmol/mg, P < 0.01). The MELD score was not significantly different between methylated and unmethylated patients with liver failure (P > 0.05), although MDA adducts were correlated with MELD scores in patients with acute-on-chronic liver failure (r = 0.579, P < 0.01). GSTP1 promoter methylation may facilitate oxidative stress-associated liver damage in ACHBLF, and oxidative stress is correlated with ACHBLF severity.