Dunn D L, Gillingham K J, Kramer M A, Schmidt W J, Erice A, Balfour H H, Gores P F, Gruessner R W, Matas A J, Payne W D
Department of Surgery, University of Minnesota, Minneapolis 55455.
Transplantation. 1994 Mar 27;57(6):876-84. doi: 10.1097/00007890-199403270-00019.
Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n = 133; GCV+HIg, n = 133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n = 28, 21.0%) in the ACV group, while significantly more patients (n = 42, 31.6%) in the GCV + HIg group developed group developed CMV disease slightly later (2.83 +/- 0.70 months) than those who received GCV/HIg (2.15 +/- 0.21 months, P > 0.01). Multivariate analysis demonstrated (2.15 +/- 0.21 months, P > 0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P < 0.001), while the difference between ACV versus GCV + HIg prophylaxis was also significant (P = 0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV + HIg prophylaxis is used in this patient population.
巨细胞病毒病在实体器官移植后频繁发生，并与患者及移植器官存活率降低相关。我们推测，巨细胞病毒传播或再激活在移植后即刻或不久后便开始，且基于更昔洛韦（GCV）的短期方案将无需长期给予抗病毒药物，或许能像基于口服阿昔洛韦（ACV）的更长疗程预防方案一样有效阻断巨细胞病毒感染和疾病，甚至可能更有效。311例患者根据移植器官类型、年龄以及是否患有糖尿病进行分层，然后随机分组，分别接受长期ACV预防（移植后12周或任何抗排斥治疗后6周，口服800 mg或静脉注射400 mg，每日4次）或短期GCV（移植后或任何抗排斥治疗后，静脉注射5 mg/kg，每12小时1次，共7天）加人免疫球蛋白（HIg；Sandoglobulin或明尼苏达巨细胞病毒免疫球蛋白），移植后或任何抗排斥治疗后第1、4和7天静脉注射100 mg/kg。共有266例患者（ACV组，n = 133；GCV + HIg组，n = 133）完成方案并可进行随访。ACV组发生巨细胞病毒病的患者较少（n = 28，21. /%），而GCV + HIg组发生巨细胞病毒病的患者明显更多（n = 42，31.6%），且GCV + HIg组患者发生巨细胞病毒病的时间略晚于接受GCV/HIg治疗的患者（2.83 ± 0.70个月比2.15 ± 0.21个月，P > 0.01）。多因素分析显示（2.15 ± 0.21个月，P > 0.1）。多因素分析表明，接受抗排斥治疗、肝移植或如果受者为巨细胞病毒血清阴性则接受来自巨细胞病毒血清阳性个体的供体器官是发生巨细胞病毒病的主要危险因素（P < 0.001），而ACV与GCV + HIg预防之间的差异也具有统计学意义（P = 0.054）。然而，两个预防组在患者或移植器官的实际存活率方面未发现差异。总体而言，ACV预防在降低移植后巨细胞病毒病发生率方面似乎更有效，尽管在高危患者组中这种效果有所减弱。我们的研究结果表明，长期给予抗病毒药物可能最能预防巨细胞病毒传播或再激活，且在该患者群体中，无论使用延长疗程的ACV还是短期的GCV + HIg预防，巨细胞病毒病的主要发病情况都是需要再次住院。
