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Background
Cytomegalovirus (CMV) disease has been considered as the most important viral infection developing after solid organ transplantation (SOT). Major risk factors associated with CMV disease are the CMV serostatus (donor positive, recipient negative [D+/R−] being at the highest risk), the type of organ transplanted and the immunosuppressive regimen used. CMV disease in this population presents with viral syndrome or tissue-invasive disease, which can be life-threatening if untreated. In addition, CMV disease in SOT recipients has been associated with a number of conditions, the so-called "indirect effects," such as acute rejection and chronic allograft dysfunction. Indirect effects of CMV are thought to result from immunological dysregulation, although local damage due to residual CMV replication has been suggested as an alternative mechanism.
Current preventive strategies against CMV disease include universal prophylaxis and preemptive therapy. Universal prophylaxis consist in the administration of an antiviral drug for a given period of time, generally 3–6 months posttransplant. The preemptive approach consists in monitoring the CMV viral load and administering an antiviral drug in case of CMV detection in the blood, before the development of symptoms. Both strategies have greatly reduced CMV-associated morbidity and mortality, although the efficacy of the preemptive approach has been less well-established. Current guidelines recommend both approaches, although antiviral prophylaxis is generally preferred for high-risk patients. However, direct comparison of both strategies has been assessed only in a few small randomized controlled trials.
Key questions are unresolved regarding the prevention of CMV disease. First, a significant number of patients (approximately 20–30% of D+/R− patients) may still develop CMV disease after discontinuation of prophylaxis. This is termed "late-onset CMV disease" and some studies suggest that it remains associated with poor outcomes in SOT recipients. Second, the preemptive approach, by allowing low-grade viral replication during the early posttransplant period, may not appropriately prevent the occurrence of CMV-associated indirect effects, and therefore long-term transplant outcomes might be inferior as compared to patients receiving antiviral prophylaxis.
The clinical significance of CMV disease in the current era has not been extensively evaluated in prospective, multicenter studies. The aim of our study was to assess the incidence, risk factors and transplant outcomes associated with CMV disease in a large nationwide cohort of SOT recipients (Swiss Transplant Cohort Study [STCS]). We specifically evaluated the impact of antiviral prophylaxis and preemptive therapy on the incidence of CMV disease and transplant outcomes, taking advantage of the variable strategies used in local transplant programs.
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