A Prospective Randomized Trial Comparing Sequential Ganciclovir-High Dose Acyclovir to High Dose Acyclovir for Prevention of Cytomegalovirus Disease in Adult Liver Transplant Recipients

Abstract

Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred fortythree patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for a months after transplantation <acyclovir group) or intravenous ganciclovir (5 mglkg twice a day) for 14 days followed by high dose oral acyclovir to complete a a-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk. 3.69; 95% confidence interval. 2.07-6.56; P<O.OOOOl). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the gancielovir group <relative risk. 5.11; 95% confidence interval, 2.05-12.75; P=O.OOOl). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P=O.OO4). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P=O.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganeiclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population.

Current Management Strategies for the Prevention and Treatment of Cytomegalovirus Infection in Pediatric Transplant Recipients

“…all but D-/R-) and D+/R-heart and liver transplant recipients. [91][92][93] In some scenarios, data are contradictory as to what the appropriate duration of intravenous therapy should be. For example, while some studies have suggested that short course therapy is not adequate for high risk liver transplant recipients, [60] use of 14 days of intravenous ganciclovir prophylaxis resulted in good outcomes in pediatric liver transplant recipients.…”

Prevention and treatment of cytomegalovirus infection in organ transplant recipients

“…Most trials conducted on liver transplant recipients have not shown a benefit of acyclovir prophylaxis ( 28, 29). Two trials did show benefit in seropositive recipients ( 30, 31), who were given intravenous acyclovir for 10 days, followed by high‐dose oral acyclovir for the first 3 months after transplantation ( 30), or 2 g/day of oral acyclovir for 4 months after transplantation ( 31).…”

“…A randomized trial in Pittsburgh compared two prophylactic regimens, high‐dose oral acyclovir for 3 months versus intravenous ganciclovir for 2 weeks, followed by high‐dose oral acyclovir for 3 months ( 28). There was a decreased incidence of disease in seropositive patients, but not in high‐risk recipients, although some decreased disease severity was observed ( 28). The incidence of disease in high‐risk individuals in the ganciclovir and acyclovir groups was 50% and 65%, respectively.…”

Viral and fungal infections after liver transplantation — Part II

“…The first entails administration of an antiviral agent to all transplant recipients immediately after transplantation (i.e., universal prophylaxis). Among 143 patients randomized either to intravenous ganciclovir for 2 weeks followed by high‐dose acyclovir for 10 weeks or to 12 weeks of high‐dose acyclovir alone,12 the incidence of CMV disease was lower in the ganciclovir‐acyclovir group (9% vs. 28%). However, the effect in the subgroup of high‐risk patients (D+/R−) was less pronounced (43% vs. 64%).…”