Early differentiation between rejection and infection in liver transplant patients by serum and biliary cytokine patterns.
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.
Warlé
Michiel C
MC
Department of Surgery, University Hospital Rotterdam, 3000 CA Rotterdam, The Netherlands.
Metselaar
Herold J
HJ
Hop
Wim C J
WC
Gyssens
Inge C
IC
Kap
Marcel
M
Kwekkeboom
Jaap
J
De Rave
Sjoerd
S
Zondervan
Pieter E
PE
IJzermans
Jan N M
JN
Tilanus
Hugo W
HW
Bouma
Gerda J
GJ
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
D016207:Cytokines; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1