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。     

肾移植受者巨细胞病毒抗原监测及其临床应用

目的:探讨巨细胞病毒CMV-PP65抗原监测在CMV感染早期快速诊断及预防治疗中的作用。方法:对37例肾移植受者采用免疫过氧化物酶法检测外周血白细胞CMV-PP65抗原,术后头3个月每周1次,4～6个月每月1次,检出CMV-PP65抗原阳性者,诊断为CMV感染,出现临床症状,排除其它原因诊断为CMV病。给予更昔洛韦预防性抗病毒治疗,疗程至少3周或CMV-PP65抗原阴转后续用7～14天。CMV病给予以更昔洛韦为主的综合治疗。结果:37例受者检出CMV-PP65抗原阳性22例,CMV感染率为595(22/37)。15例抗原阴性者,无1例发生CMV病。22例CMV-PP65抗原阳性受者给予更昔洛韦治疗后20例抗原血症阴转,2例经磷甲酸钠治疗也有效清除了CMV-PP65抗原。预防性抗病毒平均疗程为(32.4±6.5)天,抗原血症阴转平均时间为(22.6±12.3)天。仅1例发展为CMV病,且治愈,无1例因CMV病死亡。1例感染再发,再次给予更昔洛韦治疗,也有效清除了抗原。结论:CMV-PP65抗原监测可用于肾移植受者术后CMV感染的早期快速诊断,特异性、敏感性高,并用于指导肾移植受者CMV感染的预防性治疗,降低了肾移植受者CMV病发病率及死亡率。     

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。     

肝移植术后巨细胞病毒性肺炎的临床特点和治疗方法

目的 探讨肝移植术后巨细胞病毒（CMV）性肺炎的临床特点和治疗方法。方法 回顾性分析2003年10月至2005年6月间施行肝移植的451例患者的临床资料，对肝移植术后CMV性肺炎的临床特点和治疗方法进行总结。结果 在451例患者中，发生CMV性肺炎7例，感染率为1．66％。CMV性肺炎的症状明显早于体征，7例患者均无明显诱因出现高热，约1周后逐渐出现干咳、气促、呼吸困难等；血氧饱和度降低，血气分析提示低氧血症；CMV pp65抗原检测均为阳性。CMV性肺炎患者采用更昔洛韦联合膦甲酸钠抗病毒治疗，同时采取停用免疫抑制剂、加用较大剂量的丙种球蛋白和适量的胸腺肽等的个体化免疫调节方案以及广谱抗生素等综合治疗方法，6例治愈，治愈率为85．7％。结论 CMV性肺炎的早期临床表现虽然缺乏特异性，但仍有规律可循，CMV pp65抗原检测法具有特异性和敏感性高的特点。采取联合抗病毒和个体化免疫调节等综合措施治疗CMV性肺炎效果确切。     

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。     

两种方案预防肝移植术后巨细胞病毒再感染的临床疗效观察

目的 分析针对性预防方案（targeted prophylaxis）和普遍性预防方案（universal prophylaxis）在预防肝移植术后巨细胞病毒（cytomegalovirus，CMV）再感染中的临床疗效。方法 回顾性分析入选本研究的62例肝移植病人的临床资料。按术后预防CMV再感染方案的不同分为A、B两组。A组（针对性预防方案）：针对高危病例术后应用更昔洛韦预防CMV再感染。B组（普遍性预防方案）：所有病例术后常规应用更昔洛韦预防CMV再感染。对两组病人的CMV再感染率、CMV再感染相关死亡率、CMV病发生率、术后平均住院时间、病人1年生存率及预防和治疗CMV再感染的相关费用作统计分析。结果 CMV再感染率为14．5％（9／62）。A组40例，术后6例（15％，6／40）发生CMV再感染，均为无临床症状的CMV活动性感染，其中5例治愈，1例死于上消化道大出血（与CMV再感染无关）。B组22例，术后3例（13．6％，3／22）发生CMV再感染，2例无临床症状病人治愈，1例CMV肝炎病人最终死于肝功能衰竭。CMV再感染率、CMV再感染相关死亡率、CMV病发生率、术后平均住院时间及病人1年生存率两组间均无明显差异（P〉0．05）。B组用于预防和治疗CMV再感染的人均费用明显高于A组（P〈0．01）。结论 肝移植术后两种方案预防CMV再感染的临床疗效相当。相比之下，针对性预防方案更为经济，适合于我国的肝移植受体。     

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.     

优先治疗和普遍预防两种方案在肾移植术后巨细胞病毒感染中的疗效比较

目的 对比分析优先治疗和普遍预防两种方案在预防和治疗肾移植术后巨细胞病毒(CMV)感染中的疗效.方法 将64例肾移植受者随机分为优先治疗组(31例)和普遍预防组(33例).两组受者肾移植术后均接受14 d预防CMV感染的基础治疗(静脉滴注更昔洛韦250 mg/d).随后,普遍预防组受者继续口服更昔洛韦至术后90 d.优先治疗组中的高危受者继续口服更昔洛韦,直至术后90d;中危受者中仅CMV pp65抗原阳性受者静脉滴注更昔洛韦,至CMV pp65抗原转阴后停药,低危受者在基础治疗后不再使用更昔洛韦.研究期为6个月,此期间监测两组受者血清CMV pp65抗原和CMV DNA,以及血常规、尿常规、肝功能、肾功能和排斥反应发生情况.结果 普遍预防组15例(45.5%)出现CMV抗原血症,有5例(15.2%)的CMV DNA负荷量持续升高,其中3例(9.1%)发展成为CMV病.优先治疗组13例(41.9%)出现CMV抗原血症,有4例(12.9%)的CMV DNA负荷量持续升高,其中2例(6.5%)发展为CMV病.普遍预防组和优先治疗组急性排斥反应发生率分别为9.1%(3/33)和9.7%(3/31);其他感染总的发生率分别为15.2%(5/33)和19.4%(6/31),差异均无统计学意义(P>0.05).两组受者移植6个月时的存活率分别为97%和100%,其血肌酐的差异也无统计学意义(P>0.05).结论 根据受者CMV感染的风险状态采取优先治疗方案能有效预防和治疗肾移植术后CMV感染,其效果与普遍预防方案相当.     

肾移植术后巨细胞病毒感染的选择性防治方案

目的 探讨根据受者风险状态采取预先治疗策略防治肾移植术后巨细胞病毒(CMV)感染的有效性和安全性.方法 60例肾移植患者随机分为普遍预防治疗组(普遍预防组)和预先控制治疗组(预先控制组),每组30例.两组肾移植术后均接受14 d的基础治疗(静脉滴注更昔洛韦250 mg/d),随后普遍预防组继续口服更昔洛韦,至术后90 d;预先控制组中的高危患者继续口服更昔洛韦,直至术后90 d,中危患者中仅CMV pp65抗原阳性者静脉滴注更昔洛韦,至CMV pp65抗原转阴后停药,低危患者在基础治疗后不再使用更昔洛韦.研究期为6个月,期间监测两组患者的CMV pp65抗原和CMV DNA,以及血常规、尿常规、肝功能、肾功能和排斥反应发生情况.结果 普遍预防组13例(43.3%,13/30)出现抗原血症,有5例(16.7%,5/30)的CMV DNA载量持续升高,其中1例(3.3%,1/30)发展成为CMV病.预先控制组14例(46.7%,14/30)出现抗原血症,有4例(13.3%,4/30)的CMV DNA载量持续升高,其中2例(6.7%,2/30)发展为CMV病.普遍预防组和预先控制组急性排斥反应发生率分别为16.7%(5/30)和6.7%(2/30);其它感染总的发生率分别为16.7%(5/30)和20%(6/30).两个组6个月时的人、肾存活率均为100%,其血肌酐的差异也无统计学意义(P＞0.05).结论 根据受者风险状态采取预先治疗策略能有效防治肾移植术后CMV感染,其效果与普遍预防策略相当.     

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.     

Monitoring of human cytomegalovirus infections in heart transplant recipients by pp65 antigenemia

BACKGROUND: Rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromized patients at risk of developing CMV disease and syndrome. The use of CMV pp65 antigenemia as a predictor of CMV syndrome and disease in heart transplant recipient after induction therapy was studied retrospectively. METHODS: One hundred and nineteen consecutive heart transplant recipients treated with induction therapy who survived more then 14 d were monitored for CMV infection. Ninety-four recipients were seropositive for CMV. Twenty-five recipients were seronegative for CMV and received grafts from seropositive donors. Pre-emptive therapy was used in seropositive patients when CMV pp65 antigenemia was greater than 50 antigen-positive cells per 2 x 10(5) peripheral blood leukocytes (PBL); prophylactic therapy was done only in seronegative recipient matched with seropositive donor. RESULTS: High-level CMV pp65 antigenemia (50 antigen-positive cells 2 x 10(5) PBL) occurred in 34% (41 of 119) of patients at a median of 44 d following transplantation. In seropositive recipients, 16% (15 of 94) of patients developed CMV invasive disease or syndrome, and in seronegative recipients 20% (5 of 25) of patients developed CMV disease or syndrome. Sixty-six per cent (62 of 94) of CMV seropositive patients were identified as not requiring pre-emptive therapy. In seropositive and seronegative recipients, the sensibility and negative predictive value of the cut-off level of 50 antigen positive cell for CMV disease and syndrome was 100%. The specificity was 79% and positive predictive value was 49%. CONCLUSION: Because of the excellent sensibility and negative predictive value of the cut-off level of 50 antigen positive cell per 2 x 10(5) PBL, application of pre-emptive therapy guided by high level of CMV pp65 antigenemia in the context of induction therapy allow to omit antiviral therapy in many at risk patients. In the context of pre-emptive and prophylactic therapy, the cut-off level of 50 antigen positive cell do not allow to predict with accuracy the development of CMV disease or syndrome.     

Treatment of hepatitis B reinfection after liver transplantation

Patients with chronic replicative hepatitis B virus (HBV) infection who undergo orthotopic liver transplantation (OLT) in the absence of prophylactic antiviral therapy have a high risk of graft reinfection. Serial monitoring of serum HBV DNA and HBV sequence analysis, especially of the polymerase and the "a" epitope of the surface antigen, may be a requisite diagnostic tool in order to provide optimal therapeutic management for inhibition of viral replication before and after OLT. Combination therapy with hepatitis B immunoglobulin (HBIG) and lamivudine has been widely adopted as an effective prophylactic treatment regimen against recurrent HBV disease. The major issue of concern has been the development of lamivudine resistance due to the emergence of mutations in the YMDD motif of the HBV DNA polymerase gene. Among newer antivirals, adefovir dipivoxil and entecavir have been demonstrated to be effective against both wild-type and lamivudine resistant mutants. Due to the availability of antiviral drugs, outcome of patient and graft survival has dramatically improved and has become similar or even better as compared to patients with non-HBV-related liver diseases.     

Deferred versus prophylactic therapy with gancyclovir for cytomegalovirus in allograft liver transplantation

OBJECTIVE: The aim of this study was to assess the efficacy of deferred versus prophylactic therapy with gancyclovir to prevent cytomegalovirus (CMV) infection or disease in liver transplantation recipients, and to alter the timing of infection or the incidences of acute rejection, chronic rejection, or death. METHODS: We retrospectively studied 89 consecutive liver transplant recipients with a minimum of 1 year follow-up. CMV early antigen detection (pp65) was performed weekly for the first 2 months and thereafter monthly for an additional 10 months. Forty-one recipients were administered prophylactic treatment and (48 recipients) deferred therapy for positive antigenemia. RESULTS: During the first year after transplantation, CMV infection or disease developed in 61% or 12.2% of those treated with prophylactic therapy and 54.1% or 31.3% of those treated with deferred therapy (P = 0.51 or P = 0.032, respectively). The mean time to CMV disease in the prophylactic group was 161 +/- 33 days compared with 82 +/- 27 days for the deferred therapy arm (P < 0.001). Subgroup analysis based on CMV serological status also showed prophylactic treatment significantly diminished CMV disease in the CMV IgG antibody negative group. No patients died in the prophylactic group, and one died in the deferred group (P = 0.54). The incidence of acute rejection episodes was 34% in the prophylactic and 46% in the deferred group (P = 0.26). Chronic rejection was observed in two recipients in the prophylactic group versus one recipient in the deferred arm (P = 0.35). CONCLUSION: Compared with deferred therapy prophylactic therapy with gancyclovir decreased CMV disease and delayed the onset of CMV disease after liver transplantation.     

Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Abstract Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i.v. ganciclovir therapy in high-risk patients (i.e., CMV donor +/ recipient -). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver -kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporin A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R -) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV - related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i.v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

Risk factors associated with cytomegalovirus-positive antigenemia in orthotopic liver transplant patients

The aim of the study was to investigate risk factors associated with cytomegalovirus (CMV)-positive antigenemia in orthotopic liver transplant (OLT) patients. Sixty-nine patients undergoing OLT during 2001 were retrospectively evaluated for CMV antigenemia during a follow-up of 6 months after transplantation for demographic variables, pretransplant donor and recipient CMV serologic status, etiology of liver disease, number of blood transfusions, and type of immunosuppression. Among the 69 patients who underwent 71 OLT in this period, 43 met study criteria. Mean age was 49.7 +/- 10.8 years and 60.5% were men. End-stage liver disease was the indication for liver transplant, except in one case. The most prevalent etiology of liver disease was hepatitis C and/or alcohol in 66% of the cases. CMV-positive status was recorded in 74% of donors and 95% of recipients. None of the CMV-negative recipients received a positive donor allograft. CMV-positive antigenemia was 84% with 12% having two episodes of infection. There was no correlation between CMV infection and age, gender, etiology of liver disease, or number of blood transfusions. However, all patients using cyclosporine had CMV-positive antigenemia compared with 61% using tacrolimus (P <.032). In this study, the incidence of CMV infection after OLT in adult patients was slightly higher than reported in literature. No risk factor was associated with CMV antigenemia; however, this study suggests a higher probability of CMV infection among patients treated with cyclosporine.     

Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i. v. ganciclovir therapy in high-risk patients (i. e., CMV donor + / recipient ?). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver – kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporine A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R ?) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV ? related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i. v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

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.