Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants.


METHODS
Randomized, multicenter, placebo-controlled, double-blind trial.


METHODS
Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation).


METHODS
One hundred forty-one liver transplant recipients completed the study.


METHODS
CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16.


METHODS
Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness.


RESULTS
Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group).


CONCLUSIONS
CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.
Snydman
D R
DR
New England Medical Center, Boston, Massachusetts.
Werner
B G
BG
Dougherty
N N
NN
Griffith
J
J
Rubin
R H
RH
Dienstag
J L
JL
Rohrer
R H
RH
Freeman
R
R
Jenkins
R
R
Lewis
W D
WD
Hammer
S
S
O'Rourke
E
E
Grady
G F
GF
Fawaz
K
K
Kaplan
M M
MM
Hoffman
M A
MA
Katz
A T
AT
Doran
M
M
D000212:Acyclovir / Q000627:therapeutic use; D000328:Adult; D000704:Analysis of Variance; D003586:Cytomegalovirus Infections / Q000401:mortality / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009894:Opportunistic Infections / Q000517:prevention & control; D011183:Postoperative Complications / Q000517:prevention & control*; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
D016756:Immunoglobulins, Intravenous; D000212:Acyclovir