High intrahepatic HHV-6 virus loads but neither CMV nor EBV are associated with decreased graft survival after diagnosis of graft hepatitis

Pischke, Sven; Gösling, Juliane; Engelmann, Ilka; Schlue, Jerome; Wölk, Benno; Jäckel, Elmar; Meyer-Heithuis, Christoph; Lehmann, Ulrich; Strassburg, Christian P.; Barg-Hock, Hannelore; Becker, Thomas; Manns, Michael P.; Schulz, Thomas; Wedemeyer, Heiner; Heim, Albert

doi:10.1016/j.jhep.2011.12.017

« Previous Next »Journal of Hepatology
Volume 56, Issue 5 , Pages 1063-1069, May 2012

High intrahepatic HHV-6 virus loads but neither CMV nor EBV are associated with decreased graft survival after diagnosis of graft hepatitis

Sven Pischke
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
- The authors contributed equally to this work.
Juliane Gösling
- Institute of Virology, Hannover Medical School, Hannover, Germany
- The authors contributed equally to this work.
Ilka Engelmann
- Institute of Virology, Hannover Medical School, Hannover, Germany
- University Lille 2, Faculty of Medicine, CHRU Laboratory of Virology EA3610, 59120 Loos-lez-Lille, France
Jerome Schlue
- Institute of Pathology, Hannover Medical School, Hannover, Germany
Benno Wölk
- Institute of Virology, Hannover Medical School, Hannover, Germany
- Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
Elmar Jäckel
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Christoph Meyer-Heithuis
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
Ulrich Lehmann
- Institute of Pathology, Hannover Medical School, Hannover, Germany
Christian P. Strassburg
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Hannelore Barg-Hock
- Department for Abdominal Surgery, Hannover Medical School, Hannover, Germany
Thomas Becker
- Department for Abdominal Surgery, Hannover Medical School, Hannover, Germany
- Present address: Department of General Surgery and Thoracic Surgery, University Hospital Schleswig–Holstein, Campus Kiel, Germany.
Michael P. Manns
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Thomas Schulz
- Institute of Virology, Hannover Medical School, Hannover, Germany
- Konsiliarlabor für HHV-6, HHV-7, EBV und HHV-8, Hannover Medical School, Hannover, Germany
Heiner Wedemeyer
- Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
Albert Heim
- Institute of Virology, Hannover Medical School, Hannover, Germany
- Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
- Corresponding author. Address: Institute of Virology, Hannover Medical School, Hannover, Germany. Tel.: +49 511 5324311; fax: +49 511 5325732.

Received 8 July 2011; received in revised form 17 November 2011; accepted 12 December 2011. published online 16 January 2012.

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, 11.27copies/1000cells) 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 23.8months). 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.

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