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 CI 1.52–8.34 and 3.23 CI 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.
Abbreviations:
HHV-6 (human herpes virus type 6), CMV (cytomegalovirus), EBV (Epstein Barr virus), HCV (hepatitis C virus), HBV (hepatitis B virus), AST (aspartate aminotransferase), ALT (alanine aminotransferase), GGT (gamma glutamyltransferase), AP (alcaline phosphatase)Keywords
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References
- CMV hepatitis after liver transplantation: incidence, clinical course, and long-term follow-up.Liver Transpl. 2002; 8: 1138-1146
- Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation.Transpl Int. 1998; 11: 336-344
- Post-transplant lymphoproliferative disorders following liver transplantation: incidence, risk factors and survival.Am J Transplant. 2006; 6: 1017-1024
- HHV-6 DNA in peripheral blood mononuclear cells after liver transplantation.J Clin Virol. 2006; 37: S76-S81
- HHV-6 and HHV-7 antigenemia related to CMV infection after liver transplantation.J Med Virol. 2006; 78: 800-805
- HHV-6A in syncytial giant-cell hepatitis.N Engl J Med. 2008; 359: 593-602
- Clinical impact of human herpesvirus 6 infection after liver transplantation.Transplantation. 2002; 73: 599-604
- Quantitative HHV-6B antigenemia test for the monitoring of transplant patients.Eur J Clin Microbiol Infect Dis. 2010; 29: 881-886
- Frequent detection of the human herpesvirus 6-specific genomes in the livers of children with various liver diseases.J Clin Microbiol. 2001; 39: 2173-2177
- The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation.Liver Transpl. 2002; 8: 651-658
- Seroprevalence of antibodies to human herpesviruses in England and Hong Kong.J Med Virol. 1994; 43: 91-96
- Seroprevalence of cytomegalovirus infection in the United States, 1988–1994.Clin Infect Dis. 2006; 43: 1143-1151
- Comparison of seroprevalences of human herpesvirus-6 and -7 in healthy blood donors from nine countries.Vox Sang. 1998; 75: 193-197
- Herpesviruses.J Clin Pathol. 1979; 32: 859-881
- Quantification of cytomegalovirus DNA levels in intestinal biopsies as a diagnostic tool for CMV intestinal disease.J Clin Virol. 2009; 46: 254-258
- Clinical relevance of transjugular liver biopsy in comparison with percutaneous and laparoscopic liver biopsy.Gastroenterol Res Pract. 2009; 2009: 947014
- Long-term results after liver transplantation.Chirurg. 2008; 79: 121-129
- Hepatology. 1997; 25: 658-663
- Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens.J Med Virol. 2008; 80: 467-477
- Quantitative temporal and spatial distribution of adenovirus type 2 correlates with disease manifestations and organ failure during disseminated infection.J Med Virol. 2008; 80: 294-297
- Human herpesvirus-6 infection is associated with adhesion molecule induction and lymphocyte infiltration in liver allografts.J Hepatol. 2002; 37: 648-654
- Human herpesvirus 6B induces phenotypic maturation without IL-10 and IL-12p70 production in dendritic cells.Scand J Immunol. 2010; 71: 431-439
- Prevalence of herpesviridae and hepatitis virus sequences in the livers of patients with fulminant hepatitis of unknown etiology in Japan.J Gastroenterol. 2002; 37: 523-530
- Human herpesvirus-6 infection: a prospective study evaluating HHV-6 DNA levels in liver from children with acute liver failure.J Med Virol. 2008; 80: 1051-1057
- Growth of human herpesvirus 6 in HEPG2 cells.Virus Res. 1996; 45: 75-85
- Human herpesvirus 6 infections after liver transplantation.World J Gastroenterol. 2009; 15: 2561-2569
- Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles.J Clin Microbiol. 2006; 44: 1571-1574
- MELD and other factors associated with survival after liver transplantation.Am J Transplant. 2004; 4: 819-825
- New prognostic model for adult-to-adult living donor liver transplant recipients.Transplant Proc. 2011; 43: 1728-1735
- MELD and other predictors of survival after liver transplantation.Clin Transplant. 2009; 23: 220-227
- Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors.Liver Transpl. 2010; 16: 943-949
- Human herpesvirus 6 infection in adult living related liver transplant recipients.Liver Transpl. 2008; 14: 100-109
- Simultaneous monitoring by real-time polymerase chain reaction of epstein-barr virus, human cytomegalovirus, and human herpesvirus-6 in juvenile and adult liver transplant recipients.Transplant Proc. 2008; 40: 3578-3582
- Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: a prospective derivation and validation cohort analysis.Transplantation. 1998; 66: 1020-1028
- Cytomegalovirus and chronic allograft rejection in liver transplantation.World J Gastroenterol. 2004; 10: 1857-1861
- Effect of cytomegalovirus infection status on first-year mortality rates among orthotopic liver transplant recipients. The Boston Center for Liver Transplantation CMVIG Study Group.Ann Intern Med. 1997; 126: 275-279
- Response of elevated Epstein-Barr virus DNA levels to therapeutic changes in pediatric liver transplant patients: 56-month follow-up and outcome.Transplantation. 2002; 74: 367-372
- Long-term persistence of immunoglobulin A (IgA) and IgM antibodies against human cytomegalovirus in solid-organ transplant recipients.Clin Diagn Lab Immunol. 1999; 6: 621-623
Article info
Publication history
Published online: January 16, 2012
Accepted:
December 12,
2011
Received in revised form:
November 17,
2011
Received:
July 8,
2011
Identification
Copyright
© 2012 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
