Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients

Abstract

grantor: University of TorontoThe early detection of cytomegalovirus (CMV) reactivation after liver transplantation may form the basis of a pre-emptive 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 copies/ml plasma, PCR had a sensitivity of 100%, 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 >0 positive cells per 150,000 examined) were 95.2%, 55.3%, 37.0% and 97.7%. Different cut-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 copies/ml (sensitivity 85.7%, specificity 86.8%, PPV 64.3%, NPV 95.7% for >5000 copies/ml). 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 per/ml compared to 3615 copies/ml 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 antigenernia 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.M.Sc