A PROSPECTIVE RANDOMIZED TRIAL COMPARING - SEQUENTIAL, GANCICLOVIR HIGH-DOSE ACYCLOVIR TO HIGH-DOSE ACYCLOVIR FOR PREVENTION OF CYTOMEGALOVIRUS DISEASE IN ADULT LIVER-TRANSPLANT RECIPIENTS

Cytomegalovirus disease is an important cause of morbidity following l iver transplantation. To date there has not been an effective prophyla xis for CMV disease after liver transplantation. One hundred forty-thr ee patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyc lovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 d ays followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection com pared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3 .69; 95% confidence interval, 2.07-6.56; P<0.00001). Of those randomiz ed, CMV disease was seen in 20 (28%) of the acyclovir group compared w ith 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confiden ce interval, 2.05-12.75; P=0.0001). The median time to onset of CMV in fection was 45 days in the acyclovir group compared with 78 days in th e ganciclovir group (P=0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganci clovir patients (P=0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive d isease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immedi ately after transplantation followed by high dose oral acyclovir for 1 0 weeks is superior to a 12-week course of high dose oral acyclovir al one for prevention of both CMV infection and CMV disease after liver t ransplantation. However, the lack of significant effect in seronegativ e recipients who received grafts from seropositive donors suggests tha t other strategies are needed to prevent CMV infection in this high ri sk population.