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.
Share Button
New comment
Comments
No comments for this article
References
1. Sarin SK, Kedarisetty CK, Abbas Z, Amarapurkar D, Bihari C, Chan AC, Chawla YK, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int 2014;8:453-471.
2. Xu L, Tu Z, Xu G, Wang Y, Pan W, Zhan X, Luo Q, et al. Epirubicin directly promotes hepatitis B virus (HBV) replication in stable HBV-expressing cell lines: a novel mechanism of HBV reactivation following anticancer chemotherapy. Mol Med Rep 2014;9:1345-1350.
3. Mikulska M, Nicolini L, Signori A, Rivoli G, Del Bono V, Raiola AM, Di Grazia C, et al. Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome. Clin Microbiol Infect 2014;20:O694-701.
4. Finkenstedt A, Nachbaur K, Zoller H, Joannidis M, Pratschke J, Graziadei IW, Vogel W. Acute-on-chronic liver failure: excellent outcomes after liver transplantation but high mortality on the wait list. Liver Transpl 2013;19:879-886.
5. Yu-Bao Zheng ZLH, Zhe Bin Wu, Min Zhang, Yu Rong Gu, Yu Jie Su, ChaoShuang Lin, Rui Hua Zhu, Bin Liang Lin, Zhi Liang Gao. Dynamic Changes of Clinical Features that Predict the Prognosis of Acute-on-Chronic Hepatitis B Liver Failure: A Retrospective Cohort Study. International Journal of Medical Sciences 2013;10:1658-1664.
6. Kamath PS, Kim WR. The model for end-stage liver disease (MELD). Hepatology 2007;45:797-805.
7. Shimizu I, Kohno N, Tamaki K, Shono M, Huang HW, He JH, Yao DF. Female hepatology: favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol 2007;13:4295-4305.
8. Hishida M1, Nomoto S, Inokawa Y, Hayashi M, Kanda M, Okamura Y, Nishikawa Y, Tanaka C, Kobayashi D, Yamada S, Nakayama G, Fujii T, Sugimoto H, Koike M, Fujiwara M, Takeda S, Kodera Y. Estrogen receptor 1 gene as a tumor suppressor gene in hepatocellular carcinoma detected by triple-combination array analysis. International Journal of Oncology 2013;43:88-94.
9. Ahlbory-Dieker DL, Stride BD, Leder G, Schkoldow J, Trolenberg S, Seidel H, Otto C, et al. DNA binding by estrogen receptor-alpha is essential for the transcriptional response to estrogen in the liver and the uterus. Mol Endocrinol 2009;23:1544-1555.
10. Giannitrapani L, Soresi M, La Spada E, Cervello M, D'Alessandro N, Montalto G. Sex Hormones and Risk of Liver Tumor. Annals of the New York Academy of Sciences 2006;1089:228-236.
11. Villa E, Baldini GM, Rossini GP, Pasquinelli C, Melegari M, Cariani E, Tata C, et al. Ethanol-induced increase in cytosolic estrogen receptors in human male liver: a possible explanation for biochemical feminization in chronic liver disease due to alcohol. Hepatology 1988;8:1610-1614.
12. Porter LE EM, Van Thiel DH, Eagon PK. Hepatic estrogen receptor in human liver disease. Gastroenterology 1987;92:735-745.
13. Nagasue N IA, Yukaya H, Ogawa Y. Estrogen receptors in hepatocellular carcinoma. cancer 1986;57:87-91.
14. Villa E, Dugani A, Moles A, Camellini L, Grottola A, Buttafoco P, Merighi A, et al. Variant liver estrogen receptor transcripts already occur at an early stage of chronic liver disease. Hepatology 1998;27:983-988.
15. Perret C. Methylation profile as a new tool for classification of hepatocellular carcinoma. J Hepatol 2011;54:602-603.
16. Gao S, Ji XF, Li F, Sun FK, Zhao J, Fan YC, Wang K. Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 predicts prognosis of acute-on-chronic hepatitis B liver failure. J Viral Hepat 2015;22:112-119.
17. Archer KJ, Mas VR, Maluf DG, Fisher RA. High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma. Mol Genet Genomics 2010;283:341-349.
18. Dai B, Geng L, Yu Y, Sui C, Xie F, Shen W, Zheng T, et al. Methylation patterns of estrogen receptor alpha promoter correlate with estrogen receptor alpha expression and clinicopathological factors in hepatocellular carcinoma. Exp Biol Med (Maywood) 2014;239:883-890.
19. Khakpour G, Pooladi A, Izadi P, Noruzinia M, Tavakkoly Bazzaz J. DNA methylation as a promising landscape: A simple blood test for breast cancer prediction. Tumour Biol 2015;36:4905-4912.
20. Joensuu EI, Abdel-Rahman WM, Ollikainen M, Ruosaari S, Knuutila S, Peltomaki P. Epigenetic signatures of familial cancer are characteristic of tumor type and family category. Cancer Res 2008;68:4597-4605.
21. Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, de Silva HJ, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2009;3:269-282.
22. Qi Xia. XD, Yimin Zhang, Yongzheng Guo, Xiaowei Xu, Qian Yang, Weibo Du, Xiaoli Liu,Yuemei Chen, Jianrong Huang, Lanjuan Li. A Modified MELD Model for Chinese Pre-ACLF and ACLF Patients and It Reveals Poor Prognosis in Pre-ACLF Patients. PLOS ONE 2013;8:e64379.
23. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009;50:661-662.
24. Shrestha SM. Liver cirrhosis and hepatocellular carcinoma in hepatic vena cava disease, a liver disease caused by obstruction of inferior vena cava. Hepatol Int 2009;3:392-402.
25. Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 2000;31:864-871.
26. Xun YH, Shi JP, Li CQ, Li D, Shi WZ, Pan QC, Guo JC, et al. Prognostic performance of a series of model for end-stage liver disease and respective Delta scores in patients with hepatitis B acute-on-chronic liver failure. Mol Med Rep 2014;9:1559-1568.
27. Sun QF, Ding JG, Xu DZ, Chen YP, Hong L, Ye ZY, Zheng MH, et al. Prediction of the prognosis of patients with acute-on-chronic hepatitis B liver failure using the model for end-stage liver disease scoring system and a novel logistic regression model. J Viral Hepat 2009;16:464-470.
28. Zheng MH, Shi KQ, Fan YC, Li H, Ye C, Chen QQ, Chen YP. A Model to Determine 3-Month Mortality Risk in Patients With Acute-on-Chronic Hepatitis B Liver Failure. Clinical Gastroenterology and Hepatology 2011;9:351-356.e353.
29. Lai J, Lin CS, Yang L, Chen SR, Zhang YQ, Ke WM. Pretreatment HBsAg level and an early decrease in MELD score predict prognosis to lamivudine treatment for HBeAg-negative acute-on-chronic liver failure. Clin Res Hepatol Gastroenterol 2014;38:331-336.
30. Zheng MH, Shi KQ, Fan YC, Li H, Ye C, Chen QQ, Chen YP. A model to determine 3-month mortality risk in patients with acute-on-chronic hepatitis B liver failure. Clin Gastroenterol Hepatol 2011;9:351-356 e353.
31. Wang SH, Yeh SH, Lin WH, Yeh KH, Yuan Q, Xia NS, Chen DS, et al. Estrogen receptor alpha represses transcription of HBV genes via interaction with hepatocyte nuclear factor 4alpha. Gastroenterology 2012;142:989-998 e984.
32. Mizoguchi Y, Takeda H, Sakagami Y, Seki S, Kobayashi K, Yamamoto S, Morisawa S. Estradiol receptors in the cytosol of peripheral blood mononuclear cells in hepatitis B virus carriers treated with interferon-alpha. Gastroenterol Jpn 1989;24:373-379.
33. Zhu R, Zhang JS, Zhu YZ, Fan J, Mao Y, Chen Q, Zhu HG. HBx-induced androgen receptor expression in HBV-associated hepatocarcinoma is independent of the methylation status of its promoter. Histol Histopathol 2011;26:23-35.
Related articles
Citation tools
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


Download to a citation manager

Download the citation for this article by clicking on one of the following citation managers:

Metrics
This article has received 995 visits.
This article has been downloaded 136 times.

Statistics from Dimensions


Statistics from Plum Analytics

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


Share
This article hasn't been rated yet.
Reader rating:
Valora este artículo:




Asociación Española de Ecografía Digestiva Sociedad Española de Endoscopia Digestiva Sociedad Española de Patología Digestiva
The Spanish Journal of Gastroenterology is the official organ of the Sociedad Española de Patología Digestiva, the Sociedad Española de Endoscopia Digestiva and the Asociación Española de Ecografía Digestiva
Cookie policy Privacy Policy Legal Notice © Copyright 2023 y Creative Commons. The Spanish Journal of Gastroenterology