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Aliment Pharmacol Ther. 2015 Aug;42(3):319-29. doi: 10.1111/apt.13271. Epub 2015 Jun 4.

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

Author information

1
Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
2
Institute of Hepatology, Shandong University, Jinan, China.
3
Department of Hepatology, Qingdao Infectious Disease Hospital, Qingdao, China.
4
Department of Hepatology, Jinan Infectious Disease Hospital, Jinan, China.

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.

PMID:
26040771
DOI:
10.1111/apt.13271
[Indexed for MEDLINE]
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