Cytomegalovirus (CMV) is the single most significant viral infection complicating liver transplantation. CMV increases the mortality of liver transplant patients and may contribute to complicating fungal or parasitic superinfection. All liver transplant recipients have a significant risk of CMV infection; the source of CMV may be either the donor organ or the many blood transfusions given during and after transplantation. The emergent nature and volume of transfusions during surgery preclude the use of CMV antibody negative blood products. There has been no effective means of prevention of CMV disease complicating liver transplantation. Our recently completed trial in kidney transplant patients at risk for primary infection demonstrated that a CMV immune globulin for intravenous administration (CMVIG-IV) reduced the risk of virologically confirmed CMV syndromes from 60% in untreated controls to 21% in CMVIG-IV recipients (p less than 0.01). The study also showed a significant reduction in neutropenia (p less than 0.01) and in fungal or parasitic complications (p equal to 0.02). In addition, there was a 76% reduction in CMV pneumonia and mortality and a 42% reduction in the rate of viremia in the CMVIG-IV group. When patients were given therapy for rejection, CMVIG-IV reduced the rate of CMV-associated serious disease from 54% in controls to 17% in globulin recipients (p equal to 0.03). Based on the success of CMVIG-IV in renal transplant patients, a randomized, placebo-controlled, double-blind trial of CMVIG-IV prophylaxis in liver transplant recipients is proposed. All liver transplant patients will be eligible for enrollment since all are at risk for CMV infection. Patients will receive either CMVIG-IV or a visually identical placebo (1% albumin with 5% sucrose). Randomization will be stratified by recipient CMV antibody status and prophylactic use of OKT3 or ATG. Final dosage regimen will be based upon pilot trial results; the schedule is planned as follows: within 72 hours of transplantation and at 2, 4, 6, 8, 12 and 16 weeks. Patients will be followed prospectively for virus isolation and CMV associated syndromes. We estimate a 60% rate of CMV disease in liver transplant recipients. We wish to test the hypothesis that CMVIG-IV will reduce the attack rate for significant CMV disease by 50%. Based on these assumptions (alpha = 0.05, beta = 0.2), we estimate a need to enroll between 30 and 40 patients in each group (one tail or two tail statistics, respectively).
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