Detrimental impact of immunosuppressive burden on clinical course in patients with Cytomegalovirus infection after liver transplantation

Abstract

IntroductionCytomegalovirus (CMV)‐infection and reactivation remain a relevant complication after liver transplantation (LT). The recipient and donor serum CMV‐IgG‐status has been established for risk stratification when choosing various pharmaceutical regimens for CMV‐prophylaxis in the last two decades. However, factors influencing course of CMV‐infection in LT remain largely unknown. In this study, the impact of immunosuppressive regimen was examined in a large cohort of patients.MethodsAll patients that underwent primary LT between 2006 and 2018 at the Charité–Universitaetsmedizin, Berlin, were included. Clinical course as well as histological and laboratory findings of patients were analyzed our prospectively maintained database. Univariate and multivariate regression analysis for impact of variables on CMV‐occurrence was conducted, and survival was examined using Kaplan–Meier analysis.ResultsOverall, 867 patients were included in the final analysis. CMV‐infection was diagnosed in 325 (37.5%) patients after transplantation. Significantly improved overall survival was observed in these patients (Log rank = 0.03). As shown by correlation and regression tree classification and regression tree analysis, the recipient/donor CMV‐IgG‐status with either positivity had the largest influence on CMV‐occurrence. Analysis of immunosuppressive burden did not reveal statistical impact on CMV‐infection, but statistically significant inverse correlation of cumulative tacrolimus trough levels and survival was found (Log rank < .001). Multivariate analysis confirmed these findings (p = .02).DiscussionCMV‐infection remains of clinical importance after LT. Undergone CMV‐infection of either recipient or donor requires prophylactic treatment. Additionally, we found a highly significant, dosage‐dependent impact of immunosuppression (IS) on long‐term outcomes for these patients, underlying the importance of minimization of IS in liver transplant recipients. image