The Influence of mTOR Inhibitors on CMV Recurrence after Whole Organ Transplantation

Abstract

INTRODUCTION: Cytomegalovirus (CMV), a member of the -herpes-virus group, is one of the most important infections after solid organ transplantation. In immunocompetent persons CMV infection is generally harmless. But in immunosuppressed patients it is responsible for serious disease and can influence morbidity and mortality. mTOR inhibitors are a new group of immunosuppressive drugs used in solid organ transplantation, represented by Sirolimus and its derivate Everolimus. Our main intent was to evaluate if there is a difference in occurrence of CMV infection in recipients treated either with Sirolimus or Everolimus. METHODS: Patients after orthotopic heart transplantation (HTX) and after orthotopic liver transplantation (LTX) transplanted between 1983 and December 2008 at the Medical University Graz, Austria, Department for Surgery, Division of Transplantation Surgery, were included in this study. Receiving either Everolimus or Sirolimus in their immunosuppressive regimen was the inclusion criteria. Data about CMV infections, CMV donor and recipient status and through levels of immunosuppression was collected retrospectively and analysed statistically. RESULTS: 2 HTX recipients (5%) and 20 LTX recipients (29%) developed CMV infection during this period. From CMV infected recipients 9,1% obtained Everolimus and 90,9% received Sirolimus. In Sirolimus treated patients CMV infection occurred significantly more often than in Everolimus treated (p=0,003). Overall, significantly more LTX patients developed CMV infection than HTX patients did. CMV serostatus of the donor or the recipients prior to transplantation had no influence on the occurrence of CMV infection. DISCUSSION: Because there are no previous studies comparing Sirolimus and Everolimus related to their effect on the occurrence of CMV infection, we could not compare our results with others. Comparing our infection rates with others, the data for Everolimus treated recipients is similar, data for Sirolimus treated does not correlate. Infection rate in our HTX and LTX recipients is different to other studies. There could also be a bias in our study due to the fact that most of LTX patients received Sirolimus and most of HTX patients Everolimus. Anyway, it is difficult to compare our results with others, because of different immunosuppressive regimens and study designs. Besides the size of our study group is too small to see a definite trend, so further investigations have to be performed.

Date of Award	2011
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Philipp Stiegler (Supervisor) & Florian Iberer (Co-supervisor)