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Κυριακή 3 Ιουλίου 2022

Risk factors for high level cytomegalovirus viremia in liver transplant recipients and associated outcomes

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Abstract

Purpose

To evaluate epidemiology, risk-factors and outcomes of high-level cytomegalovirus (CMV) viremia in liver transplant recipients.

Methods

Adult patients receiving a liver transplant between 1/1/2017-9/30/2020 were evaluated. Viral loads at UW Health Clinical Laboratories were required to allow for numerical comparison. Primary objective was incidence and outcomes of high-level (HL) CMV viremia (viral-load >100,000 IU/mL). Secondary objective was to elucidate risk factors to allow targeted interventions.

Results

209 patients met inclusion criteria; 175 kept their graft for at least 240 days. Of these 9 patients developed HL CMV, 28 developed low-level (LL CMV, viral-load 250–100,000 IU/mL) and 138 did not develop CMV viremia. When comparing these 3 groups via classic statistical methods time from transplant to viremia was similar (HL 158 ± 77 days, LL 150 ± 76 days). Clinical factors were also similar with the exception of donor seropositivity (HL 87.5%, LL 70.4%, No CMV 49.6%, p = 0.025). HL CMV was significantly associated with graft loss (p < 0.0001) on Kaplan-Meier analysis; graft loss in the LL CMV group did not differ from the No CMV group (p = 0.96)

To allow valid assessment of risk factors in the total study population (n = 209) models of time-varying covariates were used and Cox proportional hazards ratios were calculated. In this analysis HL CMV was associated with a significantly increased risk of graft loss (HR 5.6, p = 0.0016). When investigating risk factors associated with HL CMV, donor seropositivity significantly increased risk (HR 8.85, 95% CI 1.13–71.43, p = 0.038). Pre-transplant total bilirubin (HR 1.04, 95% CI 0.998–1.07, p = 0.06) trended towards significance. Recipient seronegativity, liver disease, clinical and allocation MELD, transplant surgery duration, age, sex, induction immunosuppression, and maintenance immunosuppression were not significantly associated with development of HL CMV.

Conclusion

HL CMV after liver transplant is uncommon but is associated with a significantly increased risk of graft loss that is not present in those patients who develop LL CMV or do not develop CMV viremia. Given these negative graft effects, CMV stewardship interventions targeting recipients of CMV seropositive allografts are warranted. Future larger scale studies evaluating the potential role of other factors in risk stratification are needed.

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