1 Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Switzerland. 2 Infectious Diseases and Hospital Epidemiology, University Hospital, Basel, Switzerland. 3 Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland. 4 Department of Infectious Diseases, University Hospital Bern, Bern, Switzerland. 5 Service of Infectious Diseases, University Hospital, Geneva, Switzerland. 6 Infectious Diseases Service and Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. 7 Institute of Microbiology and Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. 8 Division of Infectious Diseases and Hospital Hygiene, Kantonsspital, St. Gallen, Switzerland. 9 Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Switzerland. 10 Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Switzerland. 11 Address correspondence to: Martin Stern, M.D., Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20 4031, Basel, Switzerland.
Transplantation. 2014 Nov 15;98(9):1013-8. doi: 10.1097/TP.0000000000000160.
Cytomegalovirus (CMV) replication has been associated with more risk for solid organ graft rejection. We wondered whether this association still holds when patients at risk receive prophylactic treatment for CMV.
We correlated CMV infection, biopsy-proven graft rejection, and graft loss in 1,414 patients receiving heart (n=97), kidney (n=917), liver (n=237), or lung (n=163) allografts reported to the Swiss Transplant Cohort Study.
Recipients of all organs were at an increased risk for biopsy-proven graft rejection within 4 weeks after detection of CMV replication (hazard ratio [HR] after heart transplantation, 2.60; 95% confidence interval [CI], 1.34-4.94, P<0.001; HR after kidney transplantation, 1.58; 95% CI, 1.16-2.16, P=0.02; HR after liver transplantation, 2.21; 95% CI, 1.53-3.17, P<0.001; HR after lung transplantation, 5.83; 95% CI, 3.12-10.9, P<0.001. Relative hazards were comparable in patients with asymptomatic or symptomatic CMV infection. The CMV donor or recipient serological constellation also predicted the incidence of graft rejection after liver and lung transplantation, with significantly higher rates of rejection in transplants in which donor or recipient were CMV seropositive (non-D-/R-), compared with D- transplant or R- transplant (HR, 3.05; P=0.002 for liver and HR, 2.42; P=0.01 for lung transplants). Finally, graft loss occurred more frequently in non-D- or non-R- compared with D- transplant or R- transplant in all organs analyzed. Valganciclovir prophylactic treatment seemed to delay, but not prevent, graft loss in non-D- or non-R- transplants.
Cytomegalovirus replication and donor or recipient seroconstellation remains associated with graft rejection and graft loss in the era of prophylactic CMV treatment.
巨细胞病毒(CMV)复制与实体器官移植物排斥的风险增加有关。我们想知道,当有风险的患者接受 CMV 预防性治疗时,这种关联是否仍然存在。
我们对瑞士移植队列研究报告的 1414 例接受心脏(n=97)、肾脏(n=917)、肝脏(n=237)或肺(n=163)同种异体移植物的患者的 CMV 感染、活检证实的移植物排斥和移植物丢失进行了相关性分析。
所有器官的受者在检测到 CMV 复制后 4 周内发生活检证实的移植物排斥的风险增加(心脏移植后 HR 为 2.60;95%置信区间[CI],1.34-4.94,P<0.001;肾脏移植后 HR 为 1.58;95%CI,1.16-2.16,P=0.02;肝脏移植后 HR 为 2.21;95%CI,1.53-3.17,P<0.001;肺移植后 HR 为 5.83;95%CI,3.12-10.9,P<0.001。无症状或有症状 CMV 感染的患者中,相对危险度相似。CMV 供体或受者的血清学构成也预测了肝和肺移植后的移植物排斥发生率,与 D-移植或 R-移植相比,供体或受者 CMV 血清阳性(非 D-/R-)的移植中排斥率显著更高(HR,3.05;P=0.002 用于肝脏,HR,2.42;P=0.01 用于肺移植)。最后,在所有分析的器官中,非 D-或非 R-移植的移植物丢失发生率高于 D-或 R-移植。缬更昔洛韦预防性治疗似乎延迟而非预防非 D-或非 R-移植中的移植物丢失。
在预防性 CMV 治疗时代,CMV 复制以及供体或受者的血清学构成与移植物排斥和移植物丢失仍然相关。