Incidence of Cytomegalovirus disease and viral replication kinetics in seropositive liver transplant recipients managed under preemptive therapy in a tertiary-care center in Mexico City: a retrospective cohort study

Abstract

Background In the absence of an adequate prevention strategy, up to 20% of CMV IgG+ liver transplant recipients (LTR) will develop CMV disease. Despite improved reporting in CMV-DNAemia, there is no consensus as to what the ideal CMV-DNAemia cutoff for a successful preemptive strategy is. Each transplant centre establishes their own threshold. We aimed to determine the effectiveness of our preventive strategy in CMV IgG+ LTR, and evaluate CMV replication kinetics. Methods In this retrospective study we determined the incidence of CMV disease in the first 6 months following transplantation in CMV seropositive LTR in a tertiary-care centre in Mexico. Secondary outcomes were determining the number of patients who required preemptive therapy (treatment cutoff ≥ 4000 UI/ml), adherence to the centre’s prevention protocol and calculation of viral replication kinetics. Results One-hundred and twenty-four patients met inclusion criteria. Four patients (3.2%) developed CMV disease. Ninety-six (85%) had detectable DNAemia and 25 (22%) asymptomatic patients received preemptive therapy, none of them developed CMV disease. The highest viral loads were observed on the second posttransplant month. The number of viral load measurements decreased over time. Patients with DNAemia ≥ 4000 UI/ml had a faster viral load growth rate, shorter viral load duplication time, and higher basic reproductive number. Viral load growth rate and autoimmune hepatitis were associated with development of DNAemia ≥ 4000 UI/ml. Conclusion Cytomegalovirus disease occurred in 3.2% of the study subjects. Preemptive therapy using a threshold of CMV ≥ 4000 UI/ml was effective in reducing the incidence of end-organ disease. The viral replication parameters described in this population highlight the importance of frequent monitoring, a challenging feat for transplant programs in low- and middle-income countries.

What’s New: Updates on Cytomegalovirus in Solid Organ Transplantation

“…85 A similar study in Liver Transplant recipients demonstrated that viral load growth rate was faster and doubling time shorter in patients who developed CMV DNAemia of ≥4000 IU/mL. 86…”

“…85 A similar study in Liver Transplant recipients demonstrated that viral load growth rate was faster and doubling time shorter in patients who developed CMV DNAemia of ≥4000 IU/mL. 86 Foscarnet and cidofovir are considered second-line antivirals given their toxicity profiles (mainly nephrotoxicity). Despite hesitancy, foscarnet may be safe to use with the proper precautions and monitoring.…”

A practical guide to real‐world implementation of pre‐emptive therapy for Cytomegalovirus disease prevention in high‐risk seronegative liver transplant recipients with seropositive donors

“…12 Higher viral load thresholds above 1000 IU/mL in plasma or whole blood for AVT initiation during PET in CMV R + LTRs may also be effective. [13][14][15] prophylaxis in CMV R + LTRs is the reduction in AVT exposure (and associated costs and toxicities), and PET has not been shown to significantly reduce the incidence of CMV disease compared to prophylaxis in CMV R + LTRs, in part because the cumulative incidence of CMV disease with 3 months of valganciclovir prophylaxis is relative low, at approximately 5%. 12,16…”

“…We have found that PET using a viral load threshold of ≥250 IU (international units)/mL in plasma to be effective for CMV disease prevention and avoids the need for any CMV AVT in approximately 75% of CMV R + patients 12 . Higher viral load thresholds above 1000 IU/mL in plasma or whole blood for AVT initiation during PET in CMV R + LTRs may also be effective 13–15 . Some centers may already incorporate different CMV preventive strategies for D + R − and R + populations, 6 and familiarity with serostatus‐guided practices may mitigate confusion surrounding serostatus‐guided AVT initiation thresholds.…”

Current Perspectives on the Management of Herpesvirus Infections in Solid Organ Transplant Recipients

“…Monitoring as part of preemptive therapy is recommended at least once weekly for 3–4 months after kidney or liver transplantation and may be extended if there is an ongoing increased risk for HCMV disease [ 9 ]. Although there is no consensus for the optimal HMCV-DNAemia cut-off for initiating preemptive therapy, a recent retrospective study showed that using a threshold of ≥4000 IU/mL was effective in reducing the incidence of end-organ disease in R+ LiTR [ 24 ]. Thresholds for initiating preemptive therapy are usually defined on available assays and patient risk factors [ 9 ].…”