Cytomegalovirus infections in renal, heart, heart‐lung and liver transplantation
Cytomegalovirus infections in renal, heart, heart‐lung and liver transplantation
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肾移植、心脏移植、心肺移植和肝移植中的巨细胞病毒感染
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发表时间：
1988
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通讯作者：
R. Pollard
中科院分区：
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作者：
R. Pollard
尽管巨细胞病毒（CMV）感染在器官移植后仍相对频繁地被发现，但随着新的免疫抑制方案的使用，其严重程度有所降低。特别是，尽管抗胸腺细胞球蛋白与发病率和死亡率的增加有关，但环孢菌素A的使用导致症状性感染的频率降低。移植受者中CMV感染的几个来源是：继发于药物治疗的免疫抑制可导致移植前存在的潜伏感染的重新激活;输血，移植前红细胞输血或手术时需要的血液也可导致CMV传播和原发感染;移植的肾脏或心脏，特别是在血清阳性器官传播给血清阴性者的情况下，可以作为传播媒介。最近的数据表明，即使在血清反应阳性的受者中也可能发生器官供体CMV的传播。移植受者CMV感染的临床表现从无症状或轻度单核细胞增多综合征到严重感染不等。一般认为，移植前血清反应阴性的患者的原发性感染比再活化感染更严重。累及多个器官系统是常见的，最常见的是视网膜炎、肺炎和胃肠道表现。一个特定的巨细胞病毒感染的肾脏也已被描述，但其表现是可变的。巨细胞病毒感染与排斥反应的关系在人类移植中仍然存在争议。已经描述了与感染严重程度相关的移植受者中细胞介导的免疫应答的改变。它可以表明，有特定的赤字淋巴细胞反应巨细胞病毒抗原和/或感染的细胞移植后，特异性免疫抑制的程度可能与临床结果。此外，严重感染的患者在其疾病过程中经常具有较低的抗体滴度。多种策略已被用于试图改变移植受者中CMV感染的风险或结果。某些中心已经常规地尝试将血清阴性肾移植到血清阴性受者中。这通常仅在活体亲属移植对和肾移植中才有可能。在一项随机对照试验中，当在移植时和前14周内给予抗感染性人白细胞干扰素时，已显示出有效降低CMV感染引起的发病率和死亡率。对肾移植受者给予免疫球蛋白制剂和对心脏移植受者进行一些初步研究一直很感兴趣。管理这些材料的确切作用尚未得到证实。尽管在安慰剂对照试验中已经施用了减毒活CMV疫苗，但未观察到对症状性CMV感染的影响。二羟基丙氧基甲基鸟嘌呤的开发提供了第一种能够从感染患者的血液和尿液中消除病毒的抗病毒化合物。此外，在非对照试验中，大多数患者患有获得性免疫缺陷综合征，疗效已被建议在胃肠道和眼睛感染，也许有一些影响肺炎。这种化合物应该为患有严重CMV感染的移植受者提供治疗选择。
Although infection with cytomegalovirus (CMV) continue to be recognized relatively frequently after organ transplantation, a decrease in their severity has been described with the use of newer immunosuppressive regimens. In particular whereas antithymocyte globulin was associated with an increase in morbidity and mortality, the use of cyclosporin A has resulted in a decrease in the frequency of symptomatic infections. Several sources of CMV infection in transplant recipients are: immunosuppression secondary to drug therapy can result in reactivation of the latent infection present before transplantation; blood transfusion, either pretransplant red blood cell transfusion or blood required at the time of surgery can also result in transmission of CMV and primary infection; the transplanted kidney or heart, particularly in situations in which seropositive organs are transmitted into seronegatives can serve as the vehicle for transmission. Recent data suggest that transmission of organ donor CMV can occur even in seropositive recipients. The clinical manifestations of CMV infection in transplant recipients range from asymptomatic or mild mononucleosis syndromes to severe infection. It is generally accepted that primary infections in patients who were seronegative before transplantation are more severe than reactivated infections. Involvement of multiple organ systems has been common, with retinitis, pneumonitis and gastrointestinal manifestations occurring most commonly. A specific CMV infection of the kidney has also been described but its manifestations are variable. The association of CMV infections with rejection remains controversial in human transplantation. Alterations in cell-mediated immune responses in transplant recipients that correlate with the severity of infection have been described. It can be shown that there are specific deficits in lymphocyte responses to cytomegalovirus antigen and/or infected cells posttransplantation and that the degree of specific immunosuppression may correlate with the clinical outcome. In addition patients with severe infection frequently have lower titers of antibody during the course of their illness. Multiple strategies have been utilized in an attempt to alter the risk or outcome of CMV infections in transplant recipients. Certain centers have routinely attempted to transplant seronegative kidneys into seronegative recipients. This is usually possible only with living related transplant pairs and in renal transplantation. Human leukocyte interferon has been shown to be effective in decreasing morbidity and mortality caused by CMV infections in a randomized controlled trial when given prophylactically at the time of transplant and through the first 14 weeks. There has been interest in the administration of immunoglobulin preparations to renal transplant recipients and some preliminary studies in cardiac transplant recipients. The exact role of the administration of these materials has not been proved. Although a live-attenuated CMV vaccine has been administrated in a placebo-controlled trial no effect on symptomatic CMV infections was observed. Development of dihydroxypropoxymethylguanine has provided the first antiviral compound that is able to eliminate virus from blood and urine of symptomatically infected patients. In addition in uncontrolled trials, which enrolled mostly patients with acquired immunodeficiency syndrome, efficacy has been suggested in gastrointestinal and eye infections, with perhaps some influence in pneumonia. This compound should offer a therapeutic option for transplant recipients with severe infections with CMV.