title: Early differentiation between rejection and infection in liver transplant patients by serum and biliary cytokine patterns.
abstract: BACKGROUND
  Differentiation between acute liver graft rejection and infection remains a clinical challenge during the early posttransplantation period. Although cytokines play a pivotal role in mediating allograft rejection, previous studies demonstrate that most cytokines are not specific for liver graft rejection or infections. However, other studies suggest that adhesion molecules and cytokines in bile reflect the immunologic activity within the liver more closely. Therefore, we postulated that by combining cytokine patterns in serum and bile, early recognition of acute liver graft rejection and differentiation from infectious complications can be improved.
  
  
  METHODS
  We performed a prospective study in 45 patients who were monitored daily for clinical events and cytokine patterns in serum and bile during the first month after liver transplantation.
  
  
  RESULTS
  Soluble intercellular adhesion molecule-1 (sICAM-1) in serum and interleukin-8 in bile were specifically increased at the onset of acute rejection (P<0.001), whereas serum soluble tumor necrosis factor-receptor II was also significantly increased in patients with infectious complications and serum interleukin-6 only in patients with rejection during infection. In 68% of patients with increased sICAM-1, acute rejection was diagnosed within 10 days, whereas rejection occurred in only 26% of patients with low serum levels of sICAM-1. In patients with increased sICAM-1, the relative risk for rejection was 4.8 (P=0.009).
  
  
  CONCLUSIONS
  Cytokine patterns in bile do not provide rejection markers with higher specificity compared with serum cytokines. Daily monitoring of sICAM-1 in serum could identify patients at risk for rejection; therefore, acute liver graft rejection may be recognized earlier in those patients.
authors.affiliation: Department of Surgery, University Hospital Rotterdam, 3000 CA Rotterdam, The Netherlands.
authors.forename: Michiel C
authors.initials: MC
authors.lastname: Warlé
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Inge C
authors.initials: IC
authors.lastname: Gyssens
authors.forename: Marcel
authors.initials: M
authors.lastname: Kap
authors.forename: Jaap
authors.initials: J
authors.lastname: Kwekkeboom
authors.forename: Sjoerd
authors.initials: S
authors.lastname: De Rave
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Zondervan
authors.forename: Jan N M
authors.initials: JN
authors.lastname: IJzermans
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: Gerda J
authors.initials: GJ
authors.lastname: Bouma
mesh_terms: D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000175:diagnosis*; D001646:Bile / Q000276:immunology*; D016207:Cytokines / Q000032:analysis* / Q000097:blood; D003937:Diagnosis, Differential; D006084:Graft Rejection / Q000175:diagnosis*; D006801:Humans; D007165:Immunosuppression Therapy; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D008875:Middle Aged; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000032:analysis
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1