Prevalence of human herpesviruses in biliary fluid and their association with biliary complications after liver transplantation

Conrad Rauber,Peter Sauer,Karl Heinz Weiss,Christian Rupp,Peter Schemmer,Katja Bartelheimer,Daniel Nils Gotthardt,Paul Schnitzler,Taotao Zhou

doi:10.1186/s12876-019-1033-x

Abstract

BackgroundBeta-herpesviruses are common opportunistic pathogens that cause morbidity after liver transplantation (LT).MethodsObjective of the study was to evaluate the prevalence and correlation of herpesviruses in bile, blood and liver tissue and to investigate their association with biliary complications and retransplantation (re-LT) free survival after LT.The study design is a single-center case-control study. We performed quantative polymerase chain reaction (qPCR) for herpesvirus 1–8 DNA in bile, blood and liver tissue of 73 patients after first LT and analyzed their clinical courses retrospectively.ResultsThe median follow-up was 48 months (range 2–102), during which a total of 16 patients underwent re-LT and 11 patients died. Of the patients, 46.5% received valganciclovir prophylaxis at the time of bile sample acquisition. Cytomegalovirus (CMV) (18.3%), human herpesvirus 6 (HHV-6) (34.2%), human herpesvirus 7 (HHV-7) (20.5%) and Epstein-Barr virus (EBV) (16.4%) were highly prevalent in bile after LT, while herpes simpex virus 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV) and human herpesvirus 8 (HHV-8) were not or rarely detected in bile. Valganciclovir prophylaxis did not reduce the prevalence of HHV-6 and HHV-7 in bile, but it did reduce the presence of CMV and EBV. The presence of HHV-6 in bile was associated with non-anastomotic biliary strictures (NAS) and acute cellular rejection (ACR).ConclusionsCMV, EBV, HHV-6 and HHV-7 are more prevalent in biliary fluid than in liver biopsy or blood serum after LT. HHV-6 and HHV-7 might be associated with biliary complications after LT. Biliary fluids might be an attractive target for routine herpesvirus detection.

Highlights

Beta-herpesviruses are common opportunistic pathogens that cause morbidity after liver transplantation (LT)
A total of 16 patients underwent re-LT at a median time of 11 months, and 11 patients died during follow-up after a median time of 15.2 months, with follow-up terminating at the combined endpoint of re-LT or death
The Endoscopic retrograde cholangiography (ERC) from which bile was retrieved occurred at a median of 3.4 months after LT

Summary

Introduction

Beta-herpesviruses are common opportunistic pathogens that cause morbidity after liver transplantation (LT). Liver transplantation requires lifelong immunosuppression to prevent allograft rejection and subsequent graft failure. Human herpesviruses (HHV) 1–8 are enveloped, double-stranded DNA and human host specific viruses that proliferate in lymphocytes and neuronal or epidermal cells. They can persist lifelong in the host and reactivate under circumstances of immunosuppression. The presence of HHV-6 and HHV-7 viremia in blood after LT has inconsistently been linked to reduced graft survival. Detecting HHV-6 DNA in liver biopsies has been associated with graft hepatitis and reduced graft survival [7,8,9].

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