Aberrant GSTP1 promoter methylation predicts short‐term prognosis in acute‐on‐chronic hepatitis B liver failure. Issue 3 (4th June 2015)

• Record Type: Journal Article
• Authors: Gao, S.; Sun, F.‐K.; Fan, Y.‐C.; Shi, C.‐H.; Zhang, Z.‐H.; Wang, L.‐Y.; Wang, K.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 42:Issue 3(2015)
• Page Start: 319
• Page End: 329
• Publication Date: 2015-06-04
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.13271
• Languages: English
• ISSNs: 0269-2813

Abstract

<abstract abstract-type="main" id="apt13271-abs-0001"> <title>Summary</title> <sec id="apt13271-sec-0001" sec-type="section"> <title>Background</title> <p>Glutathione‐S‐transferase P1 (<italic>GSTP1</italic>) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute‐on‐chronic hepatitis B liver failure (ACHBLF).</p> </sec> <sec id="apt13271-sec-0002" sec-type="section"> <title>Aim</title> <p>To evaluate the methylation level of <italic>GSTP1</italic> promoter in acute‐on‐chronic hepatitis B liver failure and determine its predictive value for prognosis.</p> </sec> <sec id="apt13271-sec-0003" sec-type="section"> <title>Methods</title> <p>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. <italic>GSTP1</italic> methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained.</p> </sec> <sec id="apt13271-sec-0004" sec-type="section"> <title>Results</title> <p> <italic>GSTP1</italic> 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%; <italic>P </italic><<italic> </italic>0.01) and HC (median 0.80%, interquartile range 0.67–1.27%; <italic>P </italic><<italic> </italic>0.01). In acute‐on‐chronic hepatitis B liver failure group, nonsurvivors showed significantly higher <italic>GSTP1</italic> methylation levels (<italic>P </italic><<italic> </italic>0.05) than survivors. <italic>GSTP1</italic> methylation level was significantly correlated with total bilirubin (<italic>r</italic> = 0.29, <italic>P </italic><<italic> </italic>0.01), prothrombin time activity (<italic>r</italic> = −0.24, <italic>P </italic>=<italic> </italic>0.01) and model for end‐stage liver disease (MELD) score (<italic>r</italic> = 0.26, <italic>P </italic>=<italic> </italic>0.01). When used to predict 1‐ or 2‐month mortality of acute‐on‐chronic hepatitis B liver failure, <italic>GSTP1</italic> methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, <italic>P </italic><<italic> </italic>0.01; AUC 0.83 vs. 0.70, <italic>P </italic><<italic> </italic>0.05 respectively]. Meanwhile, patients with <italic>GSTP1</italic> methylation levels above the cut‐off points showed significantly poorer survival than those below (<italic>P </italic><<italic> </italic>0.05).</p> </sec> <sec id="apt13271-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Aberrant <italic>GSTP1</italic> 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.</p> </sec> </abstract>