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Hepatol Res. 2017 May;47(6):566-573. doi: 10.1111/hepr.12777. Epub 2016 Aug 15.

High promoter methylation levels of glutathione-S-transferase M3 predict poor prognosis of 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, Shandong University, Jinan, China.

Abstract

AIM:

This study aimed to evaluate the prognostic value of glutathione-S-transferase M3 (GSTM3) gene promoter methylation in patients with acute-on-chronic hepatitis B liver failure (ACHBLF).

METHODS:

A total of 119 patients with ACHBLF, 60 patients with chronic hepatitis B and 30 healthy controls were enrolled. We used a quantitative methylation detection technique, MethyLight, to examine the methylation levels of GSTM3 in peripheral blood mononuclear cells.

RESULTS:

The GSTM3 methylation level was significantly higher in patients with ACHBLF than those in patients with chronic hepatitis B and healthy controls (both P < 0.05). In patients with ACHBLF, GSTM3 methylation level percentage of methylated reference (PMR) positively correlated with total bilirubin, international normalized ratio, and Model for End-stage Liver Disease (MELD) score, and negatively correlated with prothrombin activity and albumin (all P < 0.05). The PMR for GSTM3 of non-survivors was significantly increased compared to that of survivors (P < 0.05). Multivariate analysis indicated that GSTM3 methylation level was one of the independent prognostic factors for 3-month mortality of ACHBLF (P = 0.000). The area under the receiver-operator characteristic curve of PMR for GSTM3 in predicting 3-month mortality of ACHBLF was not statistically different from that of MELD score (0.798 vs. 0.716, P = 0.152). However, the area under the curve of PMR for GSTM3 was significantly higher than that of MELD score in predicting 1-month mortality (0.887 vs. 0.737, P = 0.020).

CONCLUSION:

Promoter methylation levels of GSTM3 in peripheral blood mononuclear cells closely correlated with disease severity and could be used to predict prognosis of patients with ACHBLF.

KEYWORDS:

acute-on-chronic hepatitis B liver failure; methylation; prognosis; quantitative

PMID:
27442719
DOI:
10.1111/hepr.12777

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