title: High intrahepatic HHV-6 virus loads but neither CMV nor EBV are associated with decreased graft survival after diagnosis of graft hepatitis.
abstract: OBJECTIVE
  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 3.56CI 1.52-8.34 and 3.23CI 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.
authors.affiliation: Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Pischke
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Gösling
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany; University Lille 2, Faculty of Medicine, CHRU Laboratory of Virology EA3610, 59120 Loos-lez-Lille, France.
authors.forename: Ilka
authors.initials: I
authors.lastname: Engelmann
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Jerome
authors.initials: J
authors.lastname: Schlue
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany; Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors.forename: Benno
authors.initials: B
authors.lastname: Wölk
authors.affiliation: Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Jäckel
authors.affiliation: Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Meyer-Heithuis
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
authors.affiliation: Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Strassburg
authors.affiliation: Department for Abdominal Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Barg-Hock
authors.affiliation: Department for Abdominal Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.affiliation: Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany; Konsiliarlabor für HHV-6, HHV-7, EBV und HHV-8, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schulz
authors.affiliation: Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany; Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany. Electronic address: heim.albert@mh-hannover.de.
authors.forename: Albert
authors.initials: A
authors.lastname: Heim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D003587:Cytomegalovirus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000097:blood / Q000150:complications / Q000175:diagnosis; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications / Q000175:diagnosis; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000502:physiology*; D006525:Hepatitis, Viral, Human / Q000150:complications* / Q000175:diagnosis; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008099:Liver / Q000382:microbiology; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D019349:Roseolovirus Infections / Q000097:blood / Q000150:complications / Q000175:diagnosis; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology; D055815:Young Adult
chemical_list: D004279:DNA, Viral