RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity (Publication with Expression of Concern. See vol. 73, pg. 1297, 2020) (Publication with Expression of Concern. See vol. 69, pg. 1402, 2018) (Retracted article. See vol. 73, pg. 1297, 2020)

被引:227
作者
Antoine, Daniel J. [1 ]
Jenkins, Rosalind E. [1 ]
Dear, James W. [2 ,3 ]
Williams, Dominic P. [1 ]
McGill, Mitchell R. [4 ]
Sharpe, Matthew R. [5 ]
Craig, Darren G. [6 ]
Simpson, Kenneth J. [6 ]
Jaeschke, Hartmut [4 ]
Park, B. Kevin [1 ]
机构
[1] Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool L69 3GE, Merseyside, England
[2] Univ Edinburgh, Univ BHF Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland
[3] Scottish Poisons Informat Bur, NPIS Edinburgh, Edinburgh, Midlothian, Scotland
[4] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA
[5] Univ Kansas, Med Ctr, Dept Pulm & Crit Care Med, Kansas City, KS 66160 USA
[6] Royal Infirm Edinburgh NHS Trust, Scottish Liver Transplantat Unit, Edinburgh, Midlothian, Scotland
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
HHV-6; Graft survival; Liver transplantation; CMV; EBV; ACUTE LIVER-FAILURE; GROUP BOX-1 PROTEIN; CASPASE ACTIVATION; SERUM BIOMARKERS; DISEASE SEVERITY; APOPTOSIS; MICE; OXIDATION; SURVIVAL; NECROSIS;
D O I
10.1016/j.jhep.2011.12.019
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: In liver transplant recipients with graft hepatitis, the relevance of herpesviruses is not well defined. Methods: Viral loads of CMV, EBV, and HHV-6 were determined in blood and liver biopsies of 170 liver transplant recipients with graft hepatitis by quantitative PCR. Results: HHV-6-, CMV-, and EBV-DNA were detected in 58%, 14%, and 44% of the biopsies, respectively, with coinfections in 34%. High intrahepatic HHV-6 DNA levels (>75th percentile, 11.27 copies/1000 cells) and detection of HHV-6 DNAemia were significantly associated with decreased graft survival after diagnosis of graft hepatitis (p = 0.014 and p = 0.003, respectively, median follow-up was 23.8 months). Multivariate analysis confirmed high intrahepatic HHV-6 loads as an independent factor associated with reduced graft survival (adjusted hazard ratio 2.61, 95% confidence interval 1.16-5.87). Low concentrations of HHV6 DNA in the liver, indicating latent infection, did not influence graft survival. Neither CMV nor EBV (qualitative detection and high virus loads) nor acute rejection (according to the BANFF score) affected graft survival. However, patients had been treated for CMV reactivations and acute rejections in this retrospective study. High age and high bilirubin levels were the other independent factors associated with reduced graft survival (adjusted hazard ratio 3.56 Cl 1.52-8.34 and 3.23 Cl 1.50-6.96, respectively). Conclusions: High intrahepatic HHV-6-DNA levels are associated with decreased graft survival in liver transplant recipients with graft hepatitis. The significance of HHV-6 as potential etiology of graft hepatitis needs further evaluation. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1070 / 1079
页数:10
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