Key words : DNAemia, End-organ CMV disease, Graft survival, Prophylaxis

Introduction
Cytomegalovirus (CMV) infection is one of the most common opportunistic infections in solid-organ transplant recipients. After primary infection, CMV persists as a latent virus, which then serves as a reservoir for reactivation in immunocompromised patients. Reactivation of CMV can be seen as DNAemia, asymtomatic CMV infection, or CMV disease with clinical signs and symptoms.¹ Seropositivitiy of CMV is reported to range from 20% to 100% and varies by country, age, and sex.^2-5 As reported in previous studies from different regions of Turkey, CMV seroprevalence in Turkey has been reported to be over 90%.^6-8 Although effective antivirals for prophylaxis or preemptive therapy have reduced the severity and consequences of infection, CMV viremia and CMV-related disease are still concerns with regard to mortality, morbidity, and graft survival.^9-12 In this study, our goal was to determine the frequency of CMV infections during the first year after transplant.

Materials and Methods
We analyzed the first-year data of 35 liver and 217 kidney transplant recipients over 18 years of age who received transplant procedures between May 2016 and May 2020. We retrospectively analyzed age and sex of recipients, type of organ transplanted, donor type (living or deceased), occurrence of acute rejection before infection, CMV viral load, and CMV status (asymtomatic infection or disease). All living donors were blood relatives or were interspousal relations. Cytomegalovirus DNAemia, CMV syndrome, and end-organ CMV disease definitions were made according to the American Society of Transplantation guidelines.¹

Plasma CMV DNA load was calculated with the Artus CMV Rotor Gene polymerase chain reaction (PCR) kit (Qiagen) using PCR on Rotor Gene Q Instruments according to the manufacturer’s instructions. The limit of detection and quantification was determined as 100 CMV DNA IU/mL and was considered as the cut-off DNAemia.

We examined conformity of numerical variables to normal distribution with the Shapiro-Wilk test of normality. Descriptive statistics are presented as median (minimum-maximum) for numerical variables or as number (%) for categorical variables. Pearson chi-square test was used to evaluate independent categorical data, the generalized Fisher (Fisher-Freeman-Halton) exact test was used when the Pearson chi-square test was not suitable, and the Mann Whitney U test was used to determine whether there was a statistical difference between groups in terms of the distribution of numerical variables. Type I error probability was determined as α = .05 in all statistical analyses. All analyses were performed using the IBM SPSS version 25 statistical program.

Results
Our study included 217 kidney (86.1%) and 35 liver (13.9%) transplant recipients. The ratio of men-to-women was 3.8, and the median age was 41 years (range, 18-71 years). Among the 252 total patients, 51 patients (20.2%) had CMV infection during the first year after transplant: 32 (12.7%) with CMV DNAemia, 13 (5.2%) with CMV syndrome, and 6 (2.4%) with end-organ CMV diseases. Four patients were diagnosed with gastrointestinal disease by histopathology, and 2 patients were diagnosed with CMV pneumonia by bronchoscopy and radiology. Of the 51 total CMV infections, 15 (29.4%) developed in the first 6 months posttransplant.

Table 1 shows the distributions of demographic data, the type of organ transplanted, donor type (living or deceased), occurrence of acute rejection before infection, CMV viral load, and end-organ CMV diseases. The mortality rate was 0.8% in the first year.

In patients with end-organ CMV disease, the female-to-male ratio was similar (P = .647). The median age was higher in patients with organ involvement than in patients without organ involvement, but the difference was not statistically significant (P = .141). Although there was no statistically significant difference between the 2 groups in terms of transplanted organ type, donor type, or presence of rejection (P = .855, .971, and .855, respectively), patients with end-organ diseases had significantly higher viral loads (median values were 1025 vs 335 IU/mL; P = .012). Table 2 shows related factors with end-organ CMV disease.

There were only 2 deaths, and both had end-organ CMV disease.

Discussion
In solid-organ transplant recipients, CMV infection commonly occurs in the first 12 months after transplant despite administration of prophylaxis regimens.^1,13,14 In our study, the incidence of CMV infection in the first year (20.2%) was similar to results reported in the literature.^13,14 Of 51 total CMV infections, 15 (29.4%) developed in the first 6 months after transplant, with all patients under valganciclovir prophylaxis. Prior to the administration of CMV prophylaxis to all high-risk patients within the first 100 days posttransplant, more than half of the transplant patients developed early CMV infection, with approximately one-quarter developing CMV disease and mortality of nearly 20%.^9,10,15 In our study, more than two-thirds of CMV infections were late-stage infections that developed in the second 6 months after transplant, and mortality was less than 1%. These low rates were thought to be the result of use of appropriate prophylaxis, weekly viral load monitoring, and close clinical follow-up with early treatment of CMV disease when symptoms occurred.

Close clinical findings and viral load follow-up after solid-organ transplant are very important in terms of preventing end-organ CMV disease involvement. Although the absence of CMV in blood samples from transplant recipients does not always rule out CMV disease in the presence of clinical signs and symptoms, there are numerous studies that show a link between high viral load and organ involvement.^16-18 In our study, viral load was found to be significantly higher in patients with end-organ CMV disease than in patients without organ involvement in accordance with the literature. In contrast to previous research, there was no link between transplanted organ type, donor type, or the presence of concurrent rejection and organ involvement in this study.^19,20 It was thought that this was due to the small number of reported cases.

In conclusion, we found that CMV reactivations in the first year after transplant played critical roles on survival in solid-organ transplant recipients. Regular follow-up of CMV DNAemia is crucial for modifying prophylactic and preemptive antiviral regimens.

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