肾移植术后的巨细胞病毒感染及其对急性排斥反应的影响

目的 探讨肾移植受者术后活动性巨细胞病毒（ＣＭＶ）感染的发生率、感染的原因以及ＣＭＶ感染对急性排斥反应的影响。方法 检测１８７例肾移植受者和供者术前血清抗－ＣＭＶ抗体;受者术后定期检测体内ＣＭＶ ＤＮＡ、对ＣＭＶ ＤＮＡ阳性的部分患者给予抗ＣＭＶ治疗,并比较各组排斥反应的发生率。结果 无论是供者还是受者,术前如血清抗－ＣＭＶ抗体阳性,受者术后发生活动性ＣＭＶ感染者明显增多,这些患者急性排斥反应的发     

肾移植受者外周血中人疱疹病毒6型

为了检测人疱疹病毒６型（ＨＨＶ－６）在器官移植中的致病性甲状作者对１２例肾脏移植受者在经基础免疫治疗３周后，取外周血淋巴细胞与脐血淋巴细胞共同培养。结果显示，２例受示标本中见有细胞病变（ＣＰＥ），其中１株病毒经多次传代冻存后仍能产生ＣＰＥ。该杂细胞超薄切片电镜下风疱疹病毒样颗粒，感染细胞涂片抗ＨＨＶ－６单克隆抗体产生明显荧光，证实为ＨＨＶ－６。作者认为，ＨＨＶ－６可能在肾脏移植后感染，尤其在排斥反     

用多聚酶链反应检测病毒DNA诊断肾移植受者术后人巨细胞病…

应用多聚酶链反应（ＰＣＲ）技术，直接通过肾移植受者外周血白细胞检测病毒ＤＮＡ，诊断人类巨细胞病毒（ＨＣＭＶ）活性感染。结果术前所有受者及其供者ＤＮＡ检测均为阴性，术后共检出４例阳性受者。另有３例患者亦出现类似病毒感染的症状，ＤＮＡ检测为阴性，后经检查确诊为结核和霉菌感染。２例术后１年多出现发热的受者经ＤＮＡ检测，排除ＣＭＶ感染，确诊为慢性排斥反应和霉菌感染。以上结果表明，ＰＣＲ作为移植受者术后ＨＣ     

人巨细胞病毒感染对肾移植受者血清白细胞介素－6水平的影响

应用ＰＣＲ检测ＨＣＭＶ－ＤＮＡ，ＥＬＩＳＡ检测ＨＣＭＶ－ＩｇＭ、ＩｇＧ，诊断肾移植受者ＨＣＭＶ感染，６５例受者中ＨＣＭＶ感染者３９例，非感染者２６例。应用ＭＴＴ法检测受者血清ＩＬ－６生物活性，阐明了ＨＣＭＶ感染对肾移植受者血清ＩＬ－６水平的影响。结果表明：感染与非感染组间血清ＩＬ－６水平差异无显著性（Ｐ＞０．０５）；６例原发性感染者血清ＩＬ－６水平随感染时间延长呈增高及降低双相改变，表明慢性迁延性感染者血清ＩＬ－６水平降低。临床工作中监测ＨＣＭＶ感染的肾移植受者血清ＩＬ－６水平变化具有重要意义。     

用多聚酶链反应检测病毒DNA诊断肾移植受者术后人巨细胞病毒活性感染

应用多聚酶链反应（ＰＣＲ）技术，直接通过肾移植受者外周血白细胞检测病毒ＤＮＡ，诊断人类巨细胞病毒（ＨＣＭＶ）活性感染。结果术前所有受者及其供者ＤＮＡ检测均为阴性，术后共检出４例阳性受者。另有３例患者亦出现类似病毒感染的症状，ＤＮＡ检测为阴性，后经检查确诊为结核和霉菌感染。２例术后１年多出现发热的受者经ＤＮＡ检测，排除ＣＭＶ感染，确诊为慢性排斥反应和霉菌感染。以上结果表明，ＰＣＲ作为移植受者术后ＨＣＭＶ活性感染的诊断手段，简单快速，准确性高，成本低，并可用于鉴别其它细菌（如霉菌）感染或慢性排斥反应。     

人类巨细胞病毒感染对移植肾存活的影响

１９８９年４月－１９９０年１月对肾移植术后发热４０例行尿ＰＣＲ检查。其中ＨＣＭＶ－ＤＮＡ阳性１０例，ＨＣＭＶ－ＤＮＡ阴性２２例。两组存活时间相差１０月余（Ｐ＜０．０２５）。两组的１年、３年、５年存活率差别也较大。     

人巨细胞病毒感染对肾移植受者血清白细胞介素—6水平的影响

应用ＰＣＲ检测ＨＣＭＶ－ＤＮＡ，ＥＬＩＳＡ检测ＨＣＭＶ－ＩｇＭ，ＩｇＧ，诊断肾移植受者ＨＣＭＶ感染，６５例受者中ＨＣＭＶ感染者３９例，非感染者２６例。应用ＭＴＴ法检测受者血清ＩＬ－６生物活性，阐明了ＨＣＭＶ感染对肾移植受者血清ＩＬ－６水平的影响。结果表明：感染与非感染组间血清ＩＬ－６水平差异无显著性；６例原发性感染者血清ＩＬ－６水平随感染时间延长呈增高及降低双相改变，表明慢性迁延性感染者血清ＩＬ－     

免疫抑制方案对肾移植并发慢性病毒性肝炎预后的影响

１９９１至１９９４年４月中山医科大学附一医院共完成１０１例肾移植。随访时间２８．６±９．６个月。术前供受者淋巴细胞毒性试验阴性。术中及术后２天，每日用甲基泼尼松龙（ＭＰ）０．２５～０．５ｇ，同时选用二联或三联免疫抑制方案。三联方案为泼尼松（Ｐｒｅｄ）、硫唑嘌呤（Ａｚａ）加环孢素Ａ（ＣｓＡ）；Ａｚａ于术前１天开始用１ｍｇ·ｋｇ－１·ｄ－１；Ｐｒｅｄ于术后第３天开始３０ｍｇ／ｄ，３个月后开始减量，一年后减为１０ｍｇ／ｄ；ＣｓＡ一般术后第３天开始５～８ｍｇ·ｋｇ－１·ｄ－１。二联方案为Ｐｒｅｄ加ＣｓＡ…     

肾移植术后远期急性排斥反应与巨细胞病毒感染

目的探讨肾移植术后远期急性排斥反应与巨细胞病毒感染的关系。方法检测４５例移植肾有功能存活１年以上后发生急性排斥反应者外周血白细胞中巨细胞病毒ＤＮＡ（ＣＭＶＤＮＡ）,并给予激素冲击治疗,对激素冲击无效的部分患者给予更昔洛韦抗病毒治疗。结果３２例激素冲击有效,１３例无效。无效者外周血白细胞内可测到ＣＭＶＤＮＡ,８例用更昔洛韦治疗后ＣＭＶＤＮＡ转阴,２例肾功能好转,６例恢复正常,另５例未用更昔洛韦者ＣＭＶＤＮＡ持续阳性,肾功能损害加重。结论部分肾移植受者发生的远期急性排斥反应与ＣＭＶ感染有一定关系;临床上对用激素冲击治疗无效的远期急性排斥可给予抗病毒治疗     

体外循环手术前后病人血清sIL-2R水平和T淋巴细胞亚群、NK细胞的变化及临床意义

目的：通过检测心脏体外循环（ＣＰＢ）手术前后病人血清中可溶性白介素２－受体（ｓＩＬ－２Ｒ）、Ｔ细胞亚群、自然杀伤细胞（ＮＫ），观察分析心脏ＣＰＢ手术病人细胞免疫的影响及其临床意义。方法：选择２４例风心病择期换瓣病人，术前、ＣＰＢ１０分钟、ＣＰＢ２小时、术后第１天、３天、５天检测血清ｓＩＬ－２Ｒ水平、Ｔ细胞亚群及ＮＫ细胞活性。术后第１天血清ｓＩＬ－２Ｒ水平升高，ＣＯ４（辅助细胞）活性明显降低，ＣＤ４／ＣＤ８（辅助细胞／抑制细胞）比值下降，ＮＫ活性降低；并且ｓＩＬ－２Ｒ与ＣＤ４、ＮＫ活性呈负相关。结论：低温心脏ＣＰＢ手术对病人免疫机能有不良影响，临床应采取相应措施，改善术后病人的免疫机能。     

Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.     

HHV8 in renal transplant recipients

Human herpevirus 8 (HHV8) DNA sequences have been found in lesions from patients with Kaposi's sarcoma (KS) in several forms including immunosuppressed transplant patients. We wanted to study the transmission of HHV8 in kidney transplant recipients and to assess the risk of development of KS related to the viral infection in this group of patients. We tested sera of 120 renal transplant recipients with serological assay for antibodies to HHV8 antigens before transplantation and then we tested sera of 66 patients of the same group after transplantation. Antibodies were detectable in 27.5 % of the patients before transplantation. In the seropositive population 15.1 % developed KS and in the negative group 1.1 %. Analysing 66 posttransplant sera we noticed that 24 % of the seronegative patients became positive after transplantation. Our data suggest that being positive for HHV8 before transplantation could be an important risk factor for the development of KS.     

Human Herpesvirus 8 (HHV8) Transmission and Related Morbidity in Organ Recipients

The aims of the study were to assess the risk of HHV8 transmission resulting from organ transplantation, and related morbidity in liver, heart and kidney transplant recipients. Donor and recipient serologies were screened between January 1, 2004 and January 1, 2005 using HHV8 indirect immunofluorescence latent assay (latent IFA) and indirect immunofluorescent lytic assay (lytic IFA). Recipients negative for latent IFA with a donor positive for at least one test were sequentially monitored for HHV8 viremia and underwent serological tests over a period of 2 years. The results showed that among 2354 donors, HHV8 seroprevalence was 9.9% (lytic IFA) and 4.4% (latent IFA). A total of 454 organ recipients (281 renal, 116 liver and 57 heart) were monitored over a 2‐year period. Seroconversion was observed in 12 patients (cumulative incidence 28%) whose donor had positive latent IFA and in 36 patients (cumulative incidence 29%) whose donors were positive only for lytic IFA, without differences across types of transplants. Positive HHV8 viremia was detected in only 4 out of 89 liver transplant recipients during follow‐up and not in recipients of other types of transplant. Two liver transplant recipients and one kidney transplant recipient developed KS. In conclusion, although HHV8 transmission is a frequent event after organ transplantation, HHV8‐related morbidity is rather rare but can be life threatening. Donor screening is advisable for monitoring HHV8 seronegative liver transplant recipients.     

Donor‐derived Kaposi's sarcoma in a liver–kidney transplant recipient

Human herpes virus 8 (HHV‐8), also known as Kaposi's sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi's sarcoma (KS). KS can develop following organ transplantation through reactivation of the recipient's latent HHV‐8 infection, or less commonly through donor‐derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor‐derived KS in the recipient of a liver–kidney transplant. The donor had multiple risk factors for HHV‐8 infection. The KS was successfully treated by switching immunosuppression from tacrolimus to sirolimus. With an increasing number of human immunodeficiency virus (HIV)‐positive persons seeking organ transplantation and serving as organ donors for HIV‐positive recipients, HHV‐8 prevalence among donors and recipients will likely increase and with that the risk for post‐transplant KS. Predetermination of HHV‐8 status can be useful when considering organ donors and recipients with risk factors, although there are currently no validated commercial tests for HHV‐8 antibody screening.     

Persistent human herpesvirus 8 viremia before Kaposi's sarcoma development in a liver transplant recipient

HHV8 DNA has been detected in essentially all Kaposi's sarcoma (KS) lesions investigated, including those associated with transplantation. However, the possibility of human herpesvirus 8 (HHV8) detection in serum before appearing in the tumor is unknown. We therefore studied the natural history of HHV8 infection in a liver transplant recipient who developed KS 9 months after receiving the hepatic allograft. The presence of HHV8 DNA was retrospectively analyzed by using polymerase chain reaction in frozen stored follow-up serum specimens and KS tissues (skin and lymph node biopsies). Although KS was diagnosed the day +279 posttransplant by histopathological examination of KS tissues, retrospective analysis showed that HHV8 DNA was present in all successive serum specimens taken from the day +119 onward. Accordingly, asymptomatic and persistent HHV8 viremia may precede the appearance of typical KS lesions. Monitoring transplant recipients for HHV8 could be useful for developing therapeutic and prophylactic strategies.     

Sequential measurement of human herpesvirus 6 DNA with polymerase chain reaction method in pediatric living-related liver transplantation

BACKGROUND: Human herpesvirus 6 (HHV-6), a causative virus of exanthem subitum, may occasionally present with a severe clinical form in immunosuppressed patients after transplantation. In this study, HHV-6 DNA was sequentially measured with a polymerase chain reaction (PCR) method, a quick and sensitive modality in pediatric living-related liver transplantation (LTx). METHODS: Subjects consisted of 5 post-operative biliary atresia patients undergoing living-related LTx at ages from 8 months to 4 yr. Immunosuppression was performed with Tacrolimus (blood trough level 8-18 within 1 month and 5-10 ng/mL thereafter) and low-dose steroid. Specimens were peripheral blood mononuclear cells (PBMC), plasma, and liver biopsy tissue. The amount of HHV-6 DNA was semiquantified as follows: 1+, 1-10; 2+, 10-100; 3+, 100-1000; 4+, over 1000 copies/105 PBMCs. RESULTS: A total of 69 blood samples and three liver biopsies were provided for the examination. HHV-6 DNA in PBMC was positive in 2 donors and 3 recipients before LTx. Two patients with negative DNA were converted to 3+ at 2-3 wk after LTx and 3 with positive DNA remained 2+ to 3+ throughout the post-LTx period. Only 1 patient developed clinical symptoms, such as fever, liver dysfunction, petechiae, idiopathic thrombocytopenic purpura, and finally bone marrow suppression. HHV-6 DNA in the liver biopsy tissue and plasma in this patient were 4+ and 2+, respectively. CONCLUSION: HHV-6 DNA in PBMC measured by the PCR method may be persistently high in pediatric recipients after living-related LTx. Although HHV-6 DNA in PBMC may be positive in case of evident infection, positivity in PBMC may not be always associated with the clinical symptoms.     

恩替卡韦对肝移植受者血清及外周血单个核细胞内HBV DNA的抑制作用

目的 研究恩替卡韦对乙型肝炎相关性终末期肝病患者肝移植术后血清及外周血单个核细胞（PBMC）内HBV DNA的抑制作用. 方法 选取从2007年8～12月的20例HBsAg阳性肝移植受者作为研究对象（围手术期组）,给予口服恩替卡韦每天0.5 mg联合肌注乙肝免疫球蛋白作为HBV再感染的预防方案,分别于术前1 d和术后1、4、12周采用实时荧光定量PCR法检测血清及PBMC内HBV DNA定量.同时回顾性分析2006年8月至2007年8月共34例行同种异体原位肝移植,术后长期使用恩替卡韦联合肌注乙肝免疫球蛋白的患者（随访组）,随访时间4.0～22.5个月,同样的方法检测血清及PBMC内HBV DNA定量.结果 20例受者血清HBV DNA在恩替卡韦治疗12周时全部转阴.术前1 d和术后1、4、12周PBMC内HBV DNA阳性率分别为85.0%（17/20）和45.0%（9/20）、45.0%（9/20）、40.0%（8/20）,术后1周与术前比较差异有统计学意义（P=0.004）,但1周以后阳性率无显著变化;围手术期PBMC内HBV DNA定量均值分别为104.07±2.07和101.69±1.96、101.51±1.72、101.30±1.63拷贝/106细胞,同样术后1周与术前比较差异有统计学意义（P=0.01）,但随术后时间的延长,下降趋缓,术后4周后定量值的下降差异无统计学意义（P〉0.05）.随访组平均随访13.6个月,均未发现HBV再感染（血清HBV DNA均阴性）,PBMC内HBV DNA阳性率为32.4%（11/34）,定量均值101.03±0.26拷贝/106细胞.结论 恩替卡韦对肝移植术后血清及PBMC内HBV DNA均具有较好的抑制效果,但PBMC内HBV DNA下降趋势在术后4周后即维持在相对稳定状态,不能完全被清除.     

Early and Late Virological Monitoring of Cytomegalovirus, Epstein-Barr Virus, and Human Herpes Virus 6 Infections in Small Bowel/Multivisceral Transplant Recipients

Background

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the major causes of graft failure and posttransplantation mortality among small bowel and multivisceral transplantations (SB/MVT). Little is known about human herpes virus 6 (HHV-6) infections in transplant recipients.

Study Purpose

The purposes of this study were to analyze the clinical relevance of CMV, EBV, and HHV-6 infections after small bowel transplantation and to establish whether routine monitoring for HHV-6 infection should be recommended for the prevention of severe complications in this population.

Methods

Ten adult patients were monitored based on CMV, EBV, and HHV6 DNA quantifications in blood and biopsy tissue samples. Three patients were monitored for at least 5 months (early period) and 7 patients were monitored for 1 to 5 years after transplantation (late period).

Results

In the early period, despite prophylaxis all 3 patients developed symptomatic CMV infections: 1 fever/diarrhea, 1 enteritis and rejection, as well as 1 fever and pneumonia. Only 1 patient developed EBV and HHV-6 infections. The average time of onset of CMV infection was 3 months after transplantation and only 24 days for HHV6 infection. In the late period, of the 7 SB/MVT recipients only 1 developed an EBV infection at 2 years after transplantation. No CMV or HHV-6 infections were identified in any patient.

Conclusions

CMV infection is a major cause of organ disease and rejection in the early period after transplantation. EBV infection in adult recipients must be considered also in the late period, particularly in association with severe immunosuppression. Because HHV-6 infection occurs earlier than CMV/EBV, it may serve as an indicator for more intense virological surveillance.     

公民身后器官捐献肝移植术后早期细菌和真菌感染并发症的临床特点与危险因素分析

目的对比分析公民身后器官捐献与传统司法途径器官捐献肝移植术后早期受体细菌和真菌感染并发症的临床特点,探讨公民身后器官捐献肝移植受体术后感染的危险因素。 方法回顾性研究2011年1月至2013年12月间本中心实施的公民身后器官捐献肝脏供、受体（研究组）和司法途径来源器官捐献的肝移植受体病例（对照组）,比较两组受体术后细菌、真菌感染的临床特点和预后,分析术后受体感染的危险因素。 结果共纳入公民身后器官捐献肝脏供体43例;研究组受体72例,对照组受体80例。研究组受体的细菌、真菌感染总发生率显著高于对照组（47.2% vs 31.2%）（χ²=4.071,P=0.044）。研究组受体术后1周内的细菌感染率高于对照组（64.5% vs 38.2%）（χ²=6.133,P=0.018）。供体捐献前感染和开放性创伤史是术后受体感染的独立危险因素（P=0.025、0.031）。4例疑似供体来源性受体感染,占研究组总感染例数的11.8%（4/34）。 结论使用公民身后器官捐献来源器官的肝移植术后受体感染发生率显著高于传统司法途径来源,发生细菌感染的时间更早。供体器官捐献前存在感染和有开放性创伤是肝移植术后受体发生感染的危险因素。     

Human herpesvirus 6, 7, and 8 in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HHV‐6A, HHV‐6B, HHV‐7, and HHV‐8 in the pre‐ and post‐transplant period. The majority of HHV‐6 (A and B) and HHV‐7 infections in transplant recipients are asymptomatic; symptomatic disease is reported infrequently across organs. Routine screening for HHV‐6 and 7 DNAemia is not recommended in asymptomatic patients, nor is prophylaxis or preemptive therapy. Detection of viral nucleic acid by quantitative PCR in blood or CSF is the preferred method for diagnosis of HHV‐6 and HHV‐7 infection. The possibility of chromosomally integrated HHV‐6 DNA should be considered in individuals with persistently high viral loads. Antiviral therapy should be initiated for HHV‐6 encephalitis and should be considered for other manifestations of disease. HHV‐8 causes Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease and is also associated with hemophagocytic syndrome and bone marrow failure. HHV‐8 screening and monitoring may be indicated to prevent disease. Treatment of HHV‐8 related disease centers on reduction of immunosuppression and conversion to sirolimus, while chemotherapy may be needed for unresponsive disease. The role of antiviral therapy for HHV‐8 infection has not yet been defined.