Year 2017 / Volume 109 / Number 12
Original
Methylation status of the estrogen receptor 1 promoter predicts poor prognosis of acute-on-chronic hepatitis B liver failure

818-827

DOI: 10.17235/reed.2017.4426/2016

Xiao-Peng Fan, Cheng-Yun Dou, Yu-Chen Fan, Chuang-Jie Cao, Ze-Hua Zhao, Kai Wang,

Abstract
Background: Acute-on-chronic hepatitis B liver failure (ACHBLF) is an acute deteriorating liver disease and rapidly progresses to multiple organ failure. There is currently no adequate accurate predictive models of ACHBLF prognosis. Aims: To identify the methylation frequency of the estrogen receptor 1 (ESR1) promoter in ACHBLF and analyze the associated prognostic significance. Methods: Methylation-specific PCR (MSP) was used to determine the methylation frequency of the ESR1 promoter in peripheral blood mononuclear cells from a training and validation cohort of patients. The training cohort included 113 patients with ACHBLF, 73 with chronic hepatitis B (CHB) and 40 healthy controls (HCs). The validation cohort consisted of 37 patients with ACHBLF. Another 18 patients with pre-ACHBLF who progressed to ACHBLF were used to dynamically evaluate ESR1 promoter methylation changes associated with a severe clinical condition. Results: Death from ACHBLF was associated with hyperbilirubinemia, a higher score in the model for end-stage liver disease (MELD), a higher incidence of hepatic encephalopathy (HE) and an increased frequency of ESR1 promoter methylation during the 28 day follow-up. HE, MELD score and ESR1 promoter methylation were the independent risk factors associated with 28-day mortality from ACHBLF. The frequency of ESR1 promoter methylation was significantly higher than in patients with CHB and HCs. Albumin and the MELD score were significantly associated with ESR1 promoter methylation. Moreover, ESR1 promoter methylation frequency increased with ACHBLF progression. More importantly, ESR1 promoter methylation was an independent risk factor and had a high value to predict 28-day mortality from ACHBLF. Conclusions: Abnormal ESR1 methylation could be a prognostic biomarker for ACHBLF.
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Fan X, Dou C, Fan Y, Cao C, Zhao Z, Wang K, et all. Methylation status of the estrogen receptor 1 promoter predicts poor prognosis of acute-on-chronic hepatitis B liver failure. 4426/2016


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Publication history

Received: 30/04/2016

Accepted: 25/07/2017

Online First: 30/10/2017

Published: 04/12/2017

Article revision time: 439 days

Article Online First time: 548 days

Article editing time: 583 days


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