肝移植术后巨细胞病毒性肺炎的治疗策略

探讨肝移植术后巨细胞病毒（cytomegalovirus，CMV）性肺炎的治疗方法。方法回顾分析我科2003年10月至2005年6月所行的451例肝移植病人的临床资料。发生CMV肺炎的共7例。采用更昔洛韦联合磷甲酸钠联合抗CMV，结合停用免疫抑制剂、加用大剂量丙种球蛋白和适量的胸腺肽等免疫增强剂的个体化免疫调节方案，同时采用广谱抗生素预防感染和其他对症支持等综合治疗方法。结果发生CMV感染共86例，感染率为19．1％。其中CMV肺炎7例，发生率为1．66％。治愈6例，治愈率为85．7％。结论采取联合抗病毒和个体化免疫调节等综合治疗措施效果确切。     

肝移植术后巨细胞病毒肺炎的诊断和治疗

目的探讨肝移植术后巨细胞病毒（CMV）肺炎的诊断和治疗方法。方法回顾分析5例肝移植术后CMV肺炎病例。CMV肺炎的诊断主要根据临床表现、肺部x线检查和病原学检查。5例患者均接受以抗病毒和免疫调节为主的综合治疗。结果CMV肺炎的临床表现呈非特异性。其症状主要包括发热、咳嗽、呼吸困难、心率增快、疲乏、低氧血症和白细胞减少等。肺部x线检查显示问质性肺炎。患者血清中可检测到CMV抗原或抗体。4例治愈,1例死亡。治愈率为80％,死亡率为20％。结论肝移植术后CMV肺炎的临床表现呈非特异性,其诊断主要根据临床表现、肺部X线检查及病原学检查,采取以抗病毒和免疫调节为主的综合治疗有较好疗效。     

肾移植患者巨细胞病毒感染的检测

目的建立一种诊断。肾移植受者巨细胞病毒（CMV）活动性感染的简便方法，并探讨其指导临床抗病毒治疗的价值。方法运用免疫组织化学的催化信号扩增法检测肾移植患者外周血白细胞中的巨细胞病毒磷蛋白（CMV pp65）。结果100例。肾移植受者中，44例CMV pp65抗原阳性，其中29例表现出CMV病的症状，其CMV抗原指数为（72±45）／2×10^5，而15例无症状CMV pp65抗原阳性者的CMV抗原指数为（46±25）／2×10^5，二者比较，差异有统计学意义（P〈0．05）。29例CMV病患者中，27例接受抗病毒治疗，其中26例治疗后CMV pp65抗原阳性细胞减少，症状消失，另1例CMV pp65抗原阳性细胞持续不降，患者因肺部感染死亡；未经抗病毒治疗的2例患者均死亡。结论催化信号扩增法检测外周血白细胞中的CMV pp65用于诊断。肾移植术后CMV活动性感染简便、敏感，并可指导抗病毒治疗。     

肝移植术后巨细胞病毒再感染的预防与治疗

目的　探讨肝移植术后巨细胞病毒(CMV)再感染的预防、诊断及治疗。方法　回顾性分析44例原位肝移植患者的临床资料。结果　44 例中,术前43 例(97.7 %)有CMV潜伏性感染,其中6例(14.0 %)术后发生CMV再感染。6例CMV再感染患者的CMV pp65抗原均为阳性,3例CMV IgM阳性,均为无临床症状的CMV活动性感染,其中5例治愈,无一例发展为CMV病,1 例因上消化道大出血死亡。43例中,仅有7例CMV再感染高危病例接受了抗CMV感染的预防性治疗,患者在生存期内未发生CMV再感染。结论　在我国,肝移植患者术前CMV潜伏性感染的发生率较高,测定CMV pp65抗原可以早期诊断CMV再感染;对CMV再感染的高危患者进行预防性治疗可以降低术后CMV再感染的发生率;对无临床症状的CMV再感染者进行及时、规范的治疗是防止CMV病发生的关键。     

肾移植术后巨细胞病毒感染的pp67 mRNA检测及其临床意义

目的　采用核酸基础序列扩增法 (NASBA)检测巨细胞病毒晚期mRNA基因编码的基质蛋白 pp67的表达 ,探讨pp67对肾移植术后HCMV活动性感染及指导抗病毒治疗上的作用。方法　择近期 5 0例肾移植患者进行 pp67检测并随访观察 ,与现用的CMV抗原血症法比较 ,了解pp67与HCMV活动性感染及CMV病的关系。 结果　 5 0例患者中共 5例出现CMV病 ,其CMV Ag与 pp67均呈阳性 ,pp67阳性组中CMV抗原指数显著高于pp67阴性组 ,CMV Ag与pp67平均出现阳性时间无差异 ,以pp67作为抗病毒治疗指标可以明显缩短用药时间 ,pp67比CMV Ag在抗病毒治疗后更早转阴。结论　pp67更准确地反映了肾移植术后HCMV的活动性 ,能更好的指导临床抗病毒用药。     

更昔洛韦对肝移植术后巨细胞病毒感染的预防和治疗作用

目的研究更昔洛韦在预防和治疗肝移植术后巨细胞病毒（CMV）感染和CMV性肺炎中的作用和疗效。方法回顾性分析2003年10月至2005年9月完成的480例肝移植患者的临床资料，总结分析更昔洛韦在预防和治疗肝移植术后CMV感染和CMV性肺炎中的临床效果。结果肝移植术后有402例患者使用国产更昔洛b（丽科伟）预防CMV感染，其中53例术后发生CMV感染；47例患者使用进口更昔洛韦预防CMV感染，其中6例术后发生CMV感染。480肝移植患者术后有6例确诊为CMV性肺炎，使用国产更昔洛韦治疗4例，用进口更昔洛韦治疗2例；经治疗后，5例痊愈，1例出现呼吸功能衰竭死亡。结论更昔洛韦可以有效预防肝移植术后CMV感染；使用以更昔洛韦为主要抗病毒药物的综合治疗对CMV肺炎有较好疗效。     

肝移植术后巨细胞病毒感染的防治研究

目的 探讨肝移植术后患者巨细胞病毒(CMV)感染的诊治经验。方法回顾分析我科2001年1月至2002年12月期间进行的96例同种异体肝移植病例的临床资料。结果发生巨细胞病毒感染19例,均检测到CMV抗原IE-E和CMV抗原PP65,其中CMV-IgM( )8例。在CMV感染的患者中,出现呼吸窘迫3例,发热4例,黄疸2例,14例无明显症状。经更昔洛韦治疗后18例患者血CMV抗原IE．E和CMV抗原PP65转变为阴性,1例患者死于间质性肺炎。结论肝移植后CMV感染与多种因素有关,积极预防、早期治疗肝移植术后患者CMV感染至关重要,CMV抗原检测的应用能够对CMV感染患者作出早期诊断并且指导治疗,更昔洛韦能够有效治疗CMV感染。     

肾移植术后巨细胞病毒肺炎13例报告

目的：总结肾移植术后巨细胞病毒(CMV)肺炎的防治经验,探讨有效的防治措施。方法：回顾性分析13例行同种异体肾移植术后并发CMV肺炎患者的临床资料。13例均在肾移植术后2～6个月发病,均以发热、干咳起病,胸片检查均有间质性肺炎改变。13例患者中,血CMVPP65抗原阳性9例。治疗措施包括早期抗病毒治疗、撤减免疫抑制剂用量、适时使用机械通气、加强全身支持治疗等。结果：13例患者中,治愈8例(61．5%),好转3例(23．1%),死亡2例。7例术后使用更昔洛韦预防CMV感染的患者,治愈4例,好转2例,死亡1例。结论：肾移植术后加强CMV检测有利于CMV肺炎的早期诊断。术后积极预防CMV感染,早期采取以抗病毒为主的综合治疗可提高治愈率。     

巨细胞病毒即刻早期mRNA测定在肾移植后巨细胞病毒感染中的诊断价值

目的评价应用核酸基础序列扩增法(NASBA)检测巨细胞病毒(CMV)即刻早期(IE)mRNA对肾移植术后CMV活动性感染的诊断价值。方法采用NASBA法测定55例肾移植患者的外周血标本中CMVIE mRNA及pp67mRNA,免疫组化法检测CMV pp65抗原。结果55例患者中,发生有症状的CMV活动性感染者13例;IE mRNA阳性者20例,12例有CMV活动性感染,IE mRNA的敏感度、特异度、阳性预测值及阴性预测值分别为92.3%、80.9%、60.0%及97.1%。IE mRNA阳性结果出现最早,为术后(31.0±15.4)d,与pp67mRNA的(43.7±16.3)d和pp65抗原的(39.6±15.6)d相比,差异有统计学意义(P<0.05)。结论应用NASBA法检测CMV IEmRNA,能够早期、快速、准确的诊断CMV活动性感染,为临床抗病毒的治疗提供依据。     

实时定量PCR方法监测肾移植患者血浆巨细胞病毒DNA载量及其意义

目的 采用实时定量荧光PCR方法检测巨细胞病毒(CMV)DNA拷贝数,探讨病毒载量变化在诊断CMV活动性感染中的意义和指导抗病毒治疗中的作用.方法 对40例采用预排空治疗策略预防CMV病的肾移植受者同时进行CMV抗原血症(pp65)分析和病毒载量监测并进行随访,观察CMV-DNA载量和pp65在判断肾移植受者CMV活动性感染和指导抗病毒治疗中的价值.结果 264份样本中逆转录-聚合酶链反应(RT-PCR)检测57份阳性(21.59%),病毒载量水平2.648×101～5.273×105copy/ml;抗原血症分析检测48份阳性(18.18%),抗原指数1～18/5万WBC;Cohen,s-Kappa检验结果表明两种检测方法一致性良好(Kappa=0.762).25例(62.5%)患者PCR方法检测阳性,19例(47.5%)抗原血症分析阳性.病毒载量首次出现阳性时间为(13.22±14.78)d,pp65首次出现时间为(26.72±20.61)d,差异有统计学意义(P＜0.05).40例患者中4例出现CMV病,发病时间133～179 d,3例发病前pp65和CMV-DNA均为阳性,1例仅CMV-DNA阳性.结论 血浆CMV载量检测与抗原血症分析一致性良好,而敏感性较高,更准确反映肾移植术后CMV活动性,更适合用于肾移植术后预防CMV感染的预排空治疗策略.     

肾移植术后巨细胞病毒肺炎的诊治

目的：探讨肾移植术后巨细胞病毒（CMV）肺炎的发病特点及诊治方案。方法：回顾分析9例肾移植术后并发CMV肺炎患者的临床资料。结果：治愈6例,2例有效好转,但后因经济困难放弃治疗,1例无效而死亡．结论：肾移植术后3～6个月为CMV感染易感期,术前,术后加强CMVPP65抗原及CMVIgM监测对CMV肺炎的预防及早期诊断有帮助。尽早诊断、减少或停用免疫抑制剂、早期足量长疗程抗病毒治疗、加强营养、适时机械辅助砰吸的综合治疗可提高治愈率。     

The Risk Factors for Cytomegalovirus Syndrome and Tissue-invasive Cytomegalovirus Disease in Liver Transplant Recipients Who Have Cytomegalovirus Antigenemia

Cytomegalovirus (CMV) infection is not only a common complication after liver transplantation (OLT), but also a significant contributing factor to morbidity and mortality. We investigated risk factors for CMV syndrome and tissue-invasive CMV disease in CMV antigenemia patients after OLT in a CMV endemic area. CMV antigenemia was regarded to be >1 positive CMV pp65 antigen positive cell per 400,000 white blood cells. We examined the epidemiology, clinical characteristics, and laboratory findings of liver transplant patients with CMV syndrome and tissue-invasive CMV disease. The incidence of CMV syndrome among patients with CMV antigenemia was 10.5% (37/353) and that of tissue-invasive CMV disease, 3.1% (11/353). Upon multivariate analysis the risk factors for CMV syndrome and tissue-invasive CMV disease were infection, low albumin level, high total bilirubin content, and high CMV peak titer. The 1-y, 2-y, and 3-year survival rates of subjects without CMV syndrome were 96.2%, 85.4% and 82.2% versus without tissue-invasive CMV disease, 86.9%, 83.0%, and 80.1%, or 70.3%, 56.1% and 51.8% for CMV syndrome or 72.7%, 62.3%, 49.9% for tissue-invasive CMV disease. The survival curve of patients without were superior to those with CMV syndrome (P = .000). Because OLT recipients had risk factors such as infection, low albumin level, high total bilirubin content, and high CMV peak titer, they were carefully monitored and aggressively managed due to the poor survivals of patients with CMV syndrome.     

Therapeutic implication of quantitative pp65 antigen assay in living renal transplant in a high seroendemic population

Various methods have been used to diagnose cytomegalovirus (CMV) infection/disease; however, pp65 antigenemia assay has emerged as a good marker for CMV disease in a high seroendemic population. We studied the role of quantitative pp65 antigen assay in live related renal transplant recipients in a high seroendemic population. Between November 1998 and May 2003, a total of 350 blood samples from 250 symptomatic patients were tested by quantitative pp65 antigen assay; 14% of the patients tested positive. There were 5 (14%) low-positive and 30 (86%) high-positive patients. All high-positive patients had CMV disease. The response to antiviral therapy monitored by the assay was dramatic, and one low-positive patient responded to reduction in immunosuppression. In conclusion, pp65 antigen assay is a good test for diagnosing CMV disease and monitoring response to antiviral therapy in a high seroendemic population.     

Evaluation of a new method for early detection of active cytomegalovirus infections. A study in kidney transplant recipients

Abstract Early detection of active cytomegalovirus (CMV) infection after organ transplantation is necessary to start effective antiviral treatment. In the present study, blood specimens of kidney transplant recipients ( n = 38) were monitored for the expression of CMV immediate early (IE) and late (L) mRNA using nucleic acid sequence-based amplification (NASBA). Results were compared with virus isolation, pp65 antigenemia and serology. In patients developing active CMV infection, pp65 antigen and L mRNA were detected simultaneously. At the same time, positive cell culture results could be reported to the clinic. CMV was detected significantly earlier with IE NASBA than with the other assays. However, the specificity of IE NASBA is lower than that of antigenemia, late NASBA and cell culture. Early detection of IE mRNA is especially useful for patients at high risk of developing symptomatic CMV infection in order that early, adequate antiviral therapy may be started. Late NASBA can be used to monitor further development of CMV infection, comparable to antigenemia.     

Efficacy and limitations of preemptive therapy against cytomegalovirus infections in heart transplant patients

OBJECTIVES: Cytomegalovirus (CMV) disease often represents a serious complication that promotes opportunistic infections in heart transplant recipients. In this study we evaluated the impact of preemptive gancylovir therapy, guided by pp65 antigenemia on the morbidity associated with viral reactivation. PATIENTS AND METHODS: We have performed a CMV infection surveillance program since March 1999, with antigenemia pp65 determinations weekly for the first 2 months biweekly in the third months, and monthly to the sixth month. Patients with pp65 antigenemia value >/= 10 positive cells per 2 x 10(5) polymorphonuclear cells (PMN) were treated with intravenous gancyclovir followed by 1 month of oral gancyclovir. RESULTS: Among the 107 patients who underwent the virological monitoring, 80 were pp65 antigenemia-positive with preemptive therapy administered in 48 cases. Five patients displayed symptomatic CMV disease (4.7% vs 18% rate in the period of 1988 to 1998 before the introduction of virologic monitoring; P <.01). We observed only one case of gancyclovir-resistant pneumonia which was successfully treated with foscarnet. CMV recurrence in 10 patients required a second cycle of gancyclovir treatment. Our experience included 13 opportunistic infections (12.7%) with 11 antigenemia-positive. CONCLUSIONS: Preemptive therapy drastically reduces the incidence of CMV disease and the associated morbidity. Compared to universal prophylaxis, this approach may avoid unnecessary pharmacologic treatment in more than 50% of transplant recipients. Indeed, preemptive therapy does not fully prevent CMV disease, because it may manifest at the first antigenemia determination, and furthermore may select gancyclovir-resistant strains.     

Late cytomegalovirus disease following liver transplantation

The widespread use of antiviral prophylaxis or preemptive therapy among orthotopic liver transplantation (OLT) recipients has reduced the occurrence of early cytomegalovirus (CMV) disease. Late disease is increasingly reported. Little is known about CMV disease occurring beyond the first year after transplantation. The aim of this study was to evaluate the occurrence of CMV disease two or more years after OLT and to determine its risk factors and clinical features. Eighty-one consecutive OLT recipients followed for 2 years or longer after transplantation were included in the study. Data were collected on demographic and clinical variables, clinical presentation, treatment, and outcome of late CMV disease. Late CMV disease occurred in 7/81 liver recipients (8.5%) at a mean time of 5.9 years after OLT (range: 3.5--9.3, median: 6.3 years). All seven patients were women, with a mean age of 47.7 years (range: 26--60, median: 59 years). There was no association between the development of late CMV disease and the occurrence of rejection episodes, treatment with corticosteroids, or the early use of antiviral prophylaxis. Clinical presentation included fever and disturbed liver functions in all patients, one patient had concurrent CMV pneumonitis and one CMV retinitis. Though all patients responded to ganciclovir, two had recurrent disease episodes and one patient died of secondary bacterial sepsis. Late-onset CMV disease can occur several years after OLT. Although it manifests classic clinical features of early disease, it is not associated with traditional risk factors and its pathogenesis may differ from that of early disease.