Aberrant GSTP1 promoter methylation predicts short-term prognosis in acute-on-chronic hepatitis B liver failure.

Abstract

BACKGROUND:

Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF).

AIM:

To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis.

METHODS:

One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained.

RESULTS:

GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-on-chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut-off points showed significantly poorer survival than those below (P < 0.05).

CONCLUSIONS:

Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure.

• Authors: S Gao, F-K Sun, Y-C Fan, C-H Shi, Z-H Zhang, L-Y Wang, K Wang
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 42 Issue 3 Pg. 319-29 (Aug 2015) ISSN: 1365-2036 [Electronic] England
• PMID: 26040771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Glutathione Transferase
• Bilirubin

Topics

• Adult
• Bilirubin (metabolism)
• DNA Methylation
• Female
• Glutathione Transferase (genetics)
• Hepatitis B, Chronic (complications)
• Humans
• Leukocytes, Mononuclear (metabolism)
• Liver Failure (virology)
• Male
• Middle Aged
• Oxidative Stress
• Prognosis
• Promoter Regions, Genetic
• ROC Curve
• Retrospective Studies