title: Treatment of cytomegalovirus disease in solid organ transplant recipients:  markers of inflammation as predictors of outcome.
abstract: BACKGROUND
  Treatment failure or relapse is common in solid organ transplant recipients treated for cytomegalovirus (CMV) disease. Because CMV infections induce a vigorous inflammatory response, we investigated whether pretreatment levels of inflammatory markers were associated with virologic and clinical outcomes.
  
  
  METHODS
  Solid organ transplant recipients enrolled in an international multicenter trial of CMV disease treatment (the VICTOR study) were studied (n=248). Plasma levels of markers of inflammation and endothelial cell activation were assessed at baseline and during follow-up by enzyme immunoassays.
  
  
  RESULTS
  Baseline values for the chemokine CXCL16 was an independent predictor of clinical outcome (P=0.003) and was a weak independent predictor of suppression of viral load below level of detection (LOD) (P=0.013) at day 21 after initiation of treatment. Baseline levels of the long pentraxin 3 (PTX3) was an independent predictor of suppression of viral load below LOD at day 21 (P=0.002), whereas baseline levels of von Willebrand factor (vWF) was an independent predictor of clinical outcome at day 21 (P=0.008), and vWF levels at day 21 was a weak independent inflammatory predictor of viral recurrence (P=0.018).
  
  
  CONCLUSIONS
  The present study shows that the plasma levels of CXCL16, PTX3 and vWF at the start of treatment are independently associated with virologic and clinical treatment failure during anti-CMV therapy in solid organ transplant recipients. These findings suggest a link between CMV infection and inflammation that also may influence the outcome of anti-CMV therapy.
authors.affiliation: Department of Microbiology, Oslo University Hospital, Rikshospitalet, Nydalen, Oslo, Norway. halvor.rollag@rr-research.no
authors.forename: Halvor
authors.initials: H
authors.lastname: Rollag
authors.forename: Anders
authors.initials: A
authors.lastname: Asberg
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.forename: Alan G
authors.initials: AG
authors.lastname: Jardine
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pescovitz
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Bignamini
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000097:blood; D003586:Cytomegalovirus Infections / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000097:blood*; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy*; D011237:Predictive Value of Tests; D051116:Receptors, Scavenger / Q000097:blood; D000683:Serum Amyloid P-Component / Q000378:metabolism; D014180:Transplantation; D016896:Treatment Outcome; D000077562:Valganciclovir; D014841:von Willebrand Factor / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D015774:Ganciclovir; D051116:Receptors, Scavenger; D000683:Serum Amyloid P-Component; D000077562:Valganciclovir; D014841:von Willebrand Factor; D000099153:Pentraxins; C423727:CXCL16 protein, human