title: Viral factors influencing the outcome of human cytomegalovirus infection in liver transplant recipients.
abstract: BACKGROUND
  Cytomegalovirus (CMV) remains the leading viral cause of disease following orthotopic liver transplantation (OLT) despite the availability of antiviral agents for prophylaxis and therapy.
  
  
  OBJECTIVE
  Examine the viral factors that influence the outcome of CMV infection following valganciclovir prophylaxis or laboratory-guided preemptive therapy in OLT recipients.
  
  
  METHODS
  The value of valganciclovir prophylaxis and laboratory-guided preemptive therapy for the prevention of CMV infection and disease was observed in 64 OLT recipients. Prophylaxis was given to all CMV seronegative recipients receiving a liver from a seropositive donor (D+R-; n=15), and all other recipients were randomised to receive either prophylaxis (n=24) or laboratory-guided preemptive therapy (n=25). Recipients were monitored for CMV DNAemia, viral load, emergence of antiviral resistant strains and co-infections.
  
  
  RESULTS
  CMV end-organ disease and antiviral resistant strains only occurred in D+R- recipients despite the use of prophylaxis in these patients. The D+R- recipients commencing prophylaxis immediately following transplantation had better outcomes compared to those for whom prophylaxis was delayed due to renal impairment. Prophylaxis reduced the incidence of CMV DNAemia, persistent infection, and high viral loads for CMV seropositive (D-R+and D+R+) recipients, but laboratory-guided preemptive therapy effectively controlled CMV infection and prevented disease in these OLT recipients.
  
  
  CONCLUSIONS
  Delaying the commencement of valganciclovir prophylaxis may be associated with worse outcomes for high-risk OLT recipients. Laboratory-guided pre-emptive therapy remains an alternative approach for seropositive recipients at lower risk of CMV disease.
authors.affiliation: Virology Division, Department of Microbiology, SEALS, Prince of Wales Hospital, Sydney, Australia.
authors.forename: G M
authors.initials: GM
authors.lastname: Scott
authors.forename: Z
authors.initials: Z
authors.lastname: Naing
authors.forename: J
authors.initials: J
authors.lastname: Pavlovic
authors.forename: J M
authors.initials: JM
authors.lastname: Iwasenko
authors.forename: P
authors.initials: P
authors.lastname: Angus
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: W D
authors.initials: WD
authors.lastname: Rawlinson
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000473:pathology* / Q000821:virology*; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D014180:Transplantation; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir