Clinical Utility of Quantitative Cytomegalovirus Viral Load Determination for Predicting Cytomegalovirus Disease in Liver Transplant Recipients1

Abstract

The early detection of cytomegalovirus (CMV) reactivation after liver transplantation may fonn the basis of a pre-ernptive strategy for prevention of active CMV disease. We prospectively analyzed the clinical utility of weekly CMV plasma viral load determinations by quantitative PCR and the antigenemia assay in predicting CMV disease in 97 liver transplant recipients. CMV disease occurred in 21/97 (21.7%) patients a mean of 60 days post-transplant. Using a threshold of >400 copieslml plasma, PCR had a sensitivity of 100°h, specificity 47.4%, positive predictive value (PPV) 34.4 % and negative predictive value (NPV) 100% for prediction of CMV disease.Respective values for a positive antigenemia (threshold > O positive cells per 150,000 examined) were 95.2%, 55.3%, 37.0% and 97.7 %. Different eut-off points for a positive test were analyzed using receiver-operating characteristic curves. The optimal cut-off for viral load was in the range of 2000-5000 copieslml (sensitivity 85.7%, specificity 86.8%, PPV 64.3%, NPV 95.7% for > 5000 copieslrnl). The optimal cut-off for antigenemia was in the range of 4-6 positive cells/slide. Mean peak viral load in symptomatic patients was 73,715 copies perfml compared to 3615 copieslml in patients with asymptomatic CMV reactivation (p<0.001). In a multivariate logistic regression analysis of risk factors for CMV disease (CMV serostatus, acute rejection, and induction immunosuppression), peak viral load and Peak antigenemia emerged as the only significant independent predictors of CMV disease (for PCR, OR=1.40 per 1000 copy/ml increase in viral load, p=0.0001; for antigenemia OR=1.17 per 1 positive cell/slide). Plasma viral load by quantitative PCR is a useful test for predicting CMV disease, is at least as sensitive and specific as antigenemia, and could be employed as a marker in a pre-emptive strategy. Type of CMV disease in study patients Study schedule for patients enrolled in trial. ACKNOWLEDGEMENTS LIST OF FIGURES

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

“…The CMV antigenemia test is widely used for diagnosis of disease in various immunosuppressed populations [52][53][54] and has largely replaced the standard viral culture and shell vial assays due to its increased sensitivity and predictive value. Several studies have found that CMV PCR compares favorable with CMV antigenemia in terms of both concordance and quantification 42,47,[55][56][57][58] (X Bai, RH Scheuermann, J Luby, K St. George, and C Rinaldo, unpublished findings). In some studies, PCR appeared to provide for earlier anticipation of disease 41,57 and was superior for predicting recurrent disease.…”

“…Similar conclusions have been drawn from recent studies involving other immunosuppressed cohorts. 38,[42][43][44][45][46][47][48][49][50] Quantitative PCR for CMV appears to be an effective diagnostic tool in identifying patients with disease. In addition, PCR detection of DNA targets is less sensitive to sample handling than other diagnostic tests.…”

CMV: Prevention, Diagnosis and Therapy

“…CMV QNAT is the main alternative option to antigenemia (63)(64)(65)(66)(67)(68)(69). The testing requires expensive equipment and specialized expertise.…”

Pancreatic Anastomosis Leak 15 Years After Simultaneous Pancreas-Kidney Transplantation From Late-Onset Allograft Cytomegalovirus Duodenal Ulcers Presenting With Gross Hematuria

“…In general, high CMV viral loads correlate with risk of developed CMV disease. 9 However, the correlation between viral load and immunohistopathology is not well documented. 10 Our patient was not treated for CMV infection because CMV viral load was repeatedly negative.…”