Preemptive therapy for cytomegalovirus with oral ganciclovir after liver transplantation

Abstract

We appreciate the interest in our article and congratulate Dr. Singh on the excellent results and the eradication of CMV disease in the patients cited in her study. Indeed, two important issues are discussed in the letter. First, Dr. Singh commented on the number of our patients in whom the pp65-antigen test did not precede symptoms. This finding has been confirmed by other authors: antigenemia became positive before the onset of disease in only 31 of 34 patients after renal transplantation (1). In the study of liver transplant recipients that has been cited (2), at least one of five patients who developed CMV disease had a positive pp65 antigen test only at the onset of symptoms, not earlier. The second concern is the duration of our preemptive therapy. We do not think that prolonging therapy could have avoided CMV disease in our patients because CMV disease occurred within the first week of preemptive therapy in all of the three patients who developed disease. There was only one relapse of CMV disease 6 weeks after discontinuation of preemptive therapy, and this patient had been pp65-antigen negative at the end of treatment. Even with a 98-day course of oral ganciclovir as prophylaxis, CMV disease was observed in 5% of patients (3). Unfortunately, there is no information about the duration and application route of prophylaxis and preemptive therapy of the patient population shown in the table, and the number of patients on whom the percentages are based has not been defined. However, the data confirm our observations: in 1990, the rate of CMV disease without any preemptive therapy was 20%. Assuming the same incidence of CMV disease for 1996 to 2000 and taking the given incidence of 38% for CMV infection, 50% of patients have been treated unnecessarily with the preemptive approach. Eradication of CMV disease with an increasingly aggressive regimen is possible nowadays but not reasonable in our opinion. All patients who developed CMV disease in our series could be effectively treated with a 2-week course of intravenous ganciclovir without any sequelae. Because CMV disease was rare (9%) in the 739 patients who underwent transplantations between 1993 and 2000, did not cause any mortality, and did not impair patient and graft survival, we were able to abandon prophylaxis and preemptive treatment in favor of symptom-triggered treatment. Each center should decide individually if it is more important to minimize CMV disease or to avoid unnecessary prophylaxis and preemptive treatment. In parallel, more prospective, randomized trials should be performed to evaluate better diagnostic tools for preemptive therapy. Nada Rayes1