Plasma cytomegalovirus DNA load predicts outcomes in liver transplant recipients

Abstract

Objective Cytomegalovirus (CMV) infection has a significant negative impact on liver transplant (LT) recipients. We aimed to evaluate the efficacy of real‐time DNA quantitative polymerase chain reaction (qPCR) in the early detection of CMV and predicting post‐transplant outcomes. Materials and Methods This was a retrospective study that enrolled a total of 49 adult LT recipients between December 2016 and October 2019. Serial CMV qPCR were tested weekly. We used operating characteristic curve analysis to quantify qPCR replication numbers to decide the optimal threshold to predict posttransplant complications and overall survival. Results The optimal cut‐off value of 180 copies/ml (=164 IU/ml) was determined. We had 40 patients in the low qPCR group (<180 copies/ml) and nine patients in the high qPCR group (≥180 copies/ml). Higher qPCR was associated with more severe CMV disease, early allograft dysfunction, major posttransplant complications, longer ICU stays, and lower 2‐year overall survival (OS; all p < .05). In the univariate logistic regression model, persistent DNAemia ≥ 4 weeks after anti‐CMV treatment, coexisted bacterial and/or fungal infection, and high CMV qPCR ≥ 180 copies/ml with p < .100. High CMV qPCR ≥ 180 copies/ml (p = .016; hazard ratio [HR] = 19.5; 95% confidence interval [CI] = 1.73–219.49) remained to be the only independent risk factors for major complication by the multivariate analysis. The overall 2‐year OS rates were 92.5% and 66.7% in the low and the high qPCR group, respectively (p = .030). Conclusion Our findings support evidence that qPCR is effective in detecting CMV infection provides an objective perspective in predicting posttransplant outcomes. High plasma CMV DNA load (defined as CMV qPCR ≥ 180 copies/ml or 164 IU/ml) not only indicates a hazard in developing major posttransplant complications but also associates with prolonged and refractory treatment courses.

Post-Transplantation Cytomegalovirus Infection Interplays With the Development of Anastomotic Biliary Strictures After Liver Transplantation

“…In most cases, CMV infection preceded ABS diagnosis and was virally reactivated. While the relevance of CMV detection and prevention after LT has been largely established, the association between CMV infection and ABS development remains unclear ( 20 – 22 ). Among the large existing body of literature focused on ABS risk factors, very few series have found similar findings ( 23 – 25 ).…”

Human Cytomegalovirus Is Associated with Lower HCC Recurrence in Liver Transplant Patients

“…This common opportunistic pathogen incurs a more complex infectious condition in immunocompromised recipients following organ transplantation [ 35 , 36 ]. We encourage aggressive CMV treatment once it is detected due to its lethality and many potential risks in transplant recipients [ 8 ]. However, if the clinical presentation of CMV infection becomes latent, we may have some room to make our treatment policy more flexible.…”

“…The protocol for the CMV pp65 antigenemia assay was documented in our previous study [ 8 ]. In brief, a blood sample was collected and an antigenemia assay was conducted within 6 h using the MonoFluoTM Kit CMV 52206 Immunofluorescence Assay (IFA; Bio-Rad, Hercules, CA, USA).…”

“…Human cytomegalovirus (CMV), one of the most common opportunistic infections following transplantation, has been reported to increase the risk of allograft failure and compromise post-LT outcomes [ 6 , 7 ]. A high plasma CMV DNA load indicates a risk of developing major post-transplant complications [ 8 ]. Interestingly, recent studies have revealed that CMV has potential oncolytic activity, inducing apoptosis and stimulating immune cell infiltration in the tumor microenvironment [ 9 ].…”

Cytomegalovirus infection in liver-transplanted children

“…Gerna et al [ 31 ] found that CMV disease developed in patients with a mean blood CMV viral load of 1740 copies/mL. Assay of CMV DNA by real-time quantitative polymerase chain reaction (PCR)[ 32 - 34 ] showed a cut-off value of 180 copies/mL (164 IU/mL) is associated with an increased incidence of severe CMV disease in adult liver transplant recipients[ 35 ]. The lack of an international reference standard limits the generalization of study cut-off values for worldwide use.…”