title: Differential effects of prednisolone and azathioprine on the development of human cytomegalovirus replication post liver transplantation.
abstract: BACKGROUND
  We sought to investigate the impact of different immunosuppressive regimens on human cytomegalovirus (HCMV) incidence and replication dynamics in a cohort of 256 patients after liver transplantation.
  
  
  METHODS
  A time-updated approach was used to determine the risk of developing HCMV replication (>200 genomes/mL blood) within the first 100 days after liver transplantation according to the immunosuppressive regimen being received at specific time points.
  
  
  RESULTS
  In patients receiving tacrolimus, the addition of prednisolone was associated with a significant increased risk of HCMV replication both at baseline (relative rate of infection [RRI]=4.34; P=0.0001) and in a time-updated analysis (RRI=4.68; P=0.0001). However, the addition of azathioprine substantially reduced the risk of HCMV replication to that observed with tacrolimus alone. As expected donor/recipient HCMV serostatus was also a risk factor for viraemia. Multivariable models showed that the tacrolimus plus prednisolone regimen and donor/recipient serostatus were independent risk factors for HCMV replication. Viral replication dynamics showed that the duration of HCMV viraemia, the peak viral load, and the growth rate of HCMV were greatest in patients receiving tacrolimus plus prednisolone although these differences did not reach statistical significance.
  
  
  CONCLUSIONS
  The combination of prednisolone plus tacrolimus as baseline immunosuppression after liver transplantation is associated with a high risk of HCMV replication. This effect can be negated by the addition of azathioprine.
authors: Department of Infection, Royal Free and University College Medical School, London, UK.
authors: Gaia
authors: G
authors: Nebbia
authors: Frank M
authors: FM
authors: Mattes
authors: Caroline A
authors: CA
authors: Sabin
authors: Dimitrios
authors: D
authors: Samonakis
authors: Nancy
authors: N
authors: Rolando
authors: Andrew K
authors: AK
authors: Burroughs
authors: Vincent C
authors: VC
authors: Emery
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D011239:Prednisolone; D001379:Azathioprine