High promoter methylation levels of glutathione‐S‐transferase M3 predict poor prognosis of acute‐on‐chronic hepatitis B liver failure

Sun, Feifei; Gao, Shuai; Fan, Yu–Chen; Shi, Chao; Zhang, Zhaohua; Wang, Liyuan; Li, Feng; Li, Xin-You; Ji, Xiang‐Fen; Zhao, Jing; Wang, Kai

doi:10.1111/hepr.12777

Cited by 9 publications

(8 citation statements)

References 34 publications

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“…HMGM1, OPN, and miR-122 could act as inflammatory factors in APAP-related liver injury. Further, antituberculosis DILI was found to be associated with an increase in SDH, BAs, and anti-CYP450 antibodies and patients with GSTM1, GSTP1 or HLA-DQB1*05/*05 genotypes are more likely to develop liver injury (Pauli-Magnus et al, 2005;Metushi et al, 2012;Cai et al, 2015;Chen et al, 2015;Metushi et al, 2016;Wu et al, 2016a;Sun et al, 2017). Moreover, SDH was elevated in acute and mild liver injuries and BAs have been detected in various hepatobiliary diseases.…”

Section: Future Prospects and Studiesmentioning

confidence: 97%

“…• The genetic polymorphism of GST is closely related to ATDILI and GSTa presents its sensitivity in DILI. Singla et al, 2014;Cai et al, 2015;Wu et al, 2016a;Sun et al, 2017;Tsai et al, 2017 BAs • Informative about the mechanism of cholestasis caused by drugs.…”

Section: Sorbitol Dehydrogenase (Sdh)mentioning

confidence: 99%

“…Further, GST genetic polymorphisms were associated with various liver diseases. Specifically, in patients with acute-on-chronic hepatitis B liver failure (ACLF), GSTM3 gene promoter methylation levels were significantly elevated compared to those in patients with chronic hepatitis B and healthy controls, and levels of GSTM3 methylation were associated with prognosis of ACLF (Sun et al, 2017). In NAFLD, GST plasma concentration was associated with hepatic lipid deposition (Tsai et al, 2017).…”

Section: Glutathione S-transferase (Gst)mentioning

confidence: 99%

“…Basic studying data GLDH McGill et al, 2012;Harrill et al, 2012;Antoine et al, 2013;Schomaker et al, 2013;McGill et al, 2014;Singhal et al, 2014-K18 Koelink et al, 2009Possamai et al, 2013;Thulin et al, 2014;Xie et al, 2019Cummings et al, 2008SDH Harrill et al, 2012Metushi et al, 2012Metushi et al, 2014bGST Sun et al, 2008Singla et al, 2014;Cai et al, 2015;Wu et al, 2016a;Sun et al, 2017;Yang et al, 2019Giffen et al, 2002Bailey et al, 2012;Tsai et al, 2017BAs James et al, 2015Longo et al, 2019Yamazaki et al, 2013Qiu et al, 2016;Cepa et al, 2018CYP450 Sun et al, 2008Tang et al, 2013;Tang et al, 2013;Metushi et al, 2014a;Li et al, 2014Park et al, 2016OPN Arai et al, 2006Srungaram et al, 2015He et al, 2012Arriazu et al, 2017HMGB1 Antoine et al, 2012…”

Section: Biomarker Clinical Datamentioning

confidence: 99%

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Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives

Jiang

et al. 2020

Front. Pharmacol.

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Drug-induced liver injury (DILI) is one among the common adverse drug reactions and the leading causes of drug development attritions, black box warnings, and post-marketing withdrawals. Despite having relatively low clinical incidence, its potentially severe adverse events should be considered in the individual patients due to the high risk of acute liver failure. Although traditional liver parameters have been applied to the diagnosis of DILI, the lack of specific and sensitive biomarkers poses a major limitation, and thus accurate prediction of the subsequent clinical course remains a significant challenge. These drawbacks prompt the investigation and discovery of more effective biomarkers, which could lead to early detection of DILI, and improve its diagnosis and prognosis. Novel promising biomarkers include glutamate dehydrogenase, keratin 18, sorbitol dehydrogenase, glutathione S-transferase, bile acids, cytochrome P450, osteopontin, high mobility group box-1 protein, fatty acid binding protein 1, cadherin 5, miR-122, genetic testing, and omics technologies, among others. Furthermore, several clinical scoring systems have gradually emerged for the diagnosis of DILI including the Roussel Uclaf Causality Assessment Method (RUCAM), Clinical Diagnostic Scale (CDS), and Digestive Disease Week Japan (DDW-J) systems. However, currently their predictive value is limited with certain inherent deficiencies. Thus, perhaps the greatest benefit would be achieved by simultaneously combining the scoring systems and those biomarkers. Herein, we summarized the recent research progress on molecular biomarkers for DILI to improved approaches for its diagnosis and clinical management.

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Section: Future Prospects and Studiesmentioning

confidence: 97%

Section: Sorbitol Dehydrogenase (Sdh)mentioning

confidence: 99%

Section: Glutathione S-transferase (Gst)mentioning

confidence: 99%

Section: Biomarker Clinical Datamentioning

confidence: 99%

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Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives

Jiang

et al. 2020

Front. Pharmacol.

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“…Because of its devastating effect on liver function, hepatitis B virus (HBV) poses a serious threat to the health of humans; approximately 360 million people around the world have been found to be positive for hepatitis B surface antigen (HBsAg) 1. A variety of liver diseases such as hepatocellular cirrhosis, hepatocellular carcinoma, and acute-on-chronic hepatitis B liver failure (ACHBLF) could possibly occur with the development of chronic HBV infections 2, 3. Among those liver disorders, ACHBLF is considered to be the most serious because of the acute deterioration of liver function, multiorgan failure, and high mortality rates of 50% to 90% 4-6.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid Regulates NLRP3 in Acute-On-Chronic Hepatitis B Liver Failure

Zhao

Fang

et al. 2019

Int. J. Med. Sci.

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Acute-on-chronic hepatitis B liver failure (ACHBLF) refers to the acute deterioration of liver function during chronic hepatitis B virus infection, and is associated with high mortality, with rapid progression to death. Nucleotide-binding oligomerisation domain-like receptors (NLRs) Family Pyrin Domain Containing 3(NLRP3) inflammasome contributed to the pathogenesis of D-galactosamine and lipopolysaccharide-induced acute liver failure. However, the profile of NLRP3 in patients with ACHBLF has not been demonstrated. This study was therefore conducted to investigate the expression of NLRP3 in patients with ACHBLF and identify the effect of glucocorticoid on NLRP3. We recruited 70 patients with ACHBLF undergoing glucocorticoid treatment for 28 days, 30 patients with chronic hepatitis B (CHB), and 24 healthy controls (HCs) in this study. The relative messenger RNA (mRNA) level of NLRP3 and related genes were measured by reverse transcription polymerase chain reaction, the plasma levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. The mRNA level of NLRP3 was significantly higher in patients with ACHBLF than in patients with CHB as well as HCs (P<0.05). The plasma levels of IL-1β and IL-18 in patients with ACHBLF were significantly higher than in patients with CHB and HCs (P<0.05). The relative mRNA level of NLRP3 in surviving patients decreased significantly compared with that in patients who did not survive after glucocorticoid treatment (P<0.05). In conclusion, NLRP3 increased in patients with ACHBLF. Glucocorticoid could downregulate the expression of NLRP3 in surviving patients with ACHBLF.

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Aberrant GSTP1 promoter methylation predicts poor prognosis of acute-on-chronic hepatitis B pre-liver failure

Qiao

Teng

et al. 2017

Clin Exp Med

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It has been demonstrated that glutathione-S-transferase P1 (GSTP1) could protect cells from DNA damage mediated by oxidizing agents or electrophiles in hepatic inflammatory response. Our study evaluated the methylation status and the predictive value for prognosis of GSTP1 promoter region in patients with acute-on-chronic hepatitis B pre-liver failure (pre-ACHBLF). Methylation status of GSTP1 promoter in peripheral blood mononuclear cells (PBMCs) and plasma was measured in 103 patients with pre-ACHBLF, 80 patients with chronic hepatitis B (CHB) and 30 healthy controls (HCs) by methylation-specific polymerase chain reaction. The mRNA level of GSTP1 was detected by quantitative real-time polymerase chain reaction. The methylation frequency of GSTP1 promoter region in patients with pre-ACHBLF (35/103 in PBMCs and 33/103 in plasma) was significantly higher than CHB (2/80) and HCs (0/30), respectively. The mRNA level of GSTP1 in patients with pre-ACHBLF was significantly lower than CHB and HCs. Additionally, pre-ACHBLF patients with methylated GSTP1 presented strikingly higher incidence of ACHBLF than those without. Of note, GSTP1 methylation presented distinctly better performance than model for end-stage liver disease score [area under the receiver operating characteristic curves (AUCs) 0.825 in PBMCs and 0.798 in plasma VS 0.589; AUC 0.804 in PBMCs and 0.779 in plasma VS 0.622; AUC 0.767 in PBMCs and 0.744 in plasma VS 0.602, respectively] when used to predict the 1-, 2- or 3-month incidence of ACHBLF in patients with pre-ACHBLF. Aberrant methylation of GSTP1 has potential to be a prognostic biomarker for pre-ACHBLF.

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High promoter methylation levels of glutathione‐S‐transferase M3 predict poor prognosis of acute‐on‐chronic hepatitis B liver failure

Abstract: 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.

Cited by 9 publications

References 34 publications

Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives

Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives

Glucocorticoid Regulates NLRP3 in Acute-On-Chronic Hepatitis B Liver Failure

Aberrant GSTP1 promoter methylation predicts poor prognosis of acute-on-chronic hepatitis B pre-liver failure

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