RANDOMIZED TRIAL OF EFFICACY AND SAFETY OF ORAL GANCICLOVIR IN THE PREVENTION OF CYTOMEGALOVIRUS DISEASE IN LIVER-TRANSPLANT RECIPIENTS

Background Cytomegalovirus (CMV) disease is a frequent cause of seriou s morbidity after solid-organ transplantation. The prophylactic regime ns used to prevent CMV infection and disease have shown limited benefi t in seronegative recipients. We studied the safety and efficacy of or al ganciclovir in the prevention of CMV disease following orthotopic l iver transplantation. Methods Between December, 1993, and April, 1995, 304 liver-transplant recipients were randomised to receive oral ganci clovir 1000 mg or matching placebo three times a day. Seronegative rec ipients of seronegative livers were excluded. Study drug was administe red as soon as the patient was able to take medication by mouth (no la ter than day 10) until the 98th day after transplantation. Patients we re assessed at specified times throughout the first 6 months after sur gery for evidence of CMV infection, CMV disease, rejection, opportunis tic infections, and possible drug toxicity. Findings The Kaplan-Meier estimate of the 6-month incidence of CMV disease was 29 (18.9%) of 154 in the placebo group, compared with seven (4.8%) of 150 in the gancic lovir group (p<0.001). In the high-risk group of seronegative recipien ts (R-) of seropositive livers (D+), incidence of CMV disease was 11 ( 44.0%) of 25 in the placebo group, three (14.8%) of 21 in the ganciclo vir group (p=0.02). Significant benefit was also observed in those rec eiving antibodies to lymphocytes, where the incidence of CMV disease w as 12 (32.9%) of 37 in the placebo group and two (4.6%) of 44 in the g anciclovir group (p=0.002). Oral ganciclovir reduced the incidence of CMV infection (placebo 79 [51.5%] of 154; ganciclovir 37 [24.5%] of 15 0; p<0.001) and also reduced symptomatic herpes-simplex infections (Ka plan-Meier estimates: placebo 36 [23.5%] of 154; ganciclovir five [3.5 %] of 150; p<0.001). Interpretation Oral ganciclovir is a safe and eff ective method for the prevention of CMV disease after orthotopic liver transplantation.