Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts

Thirty-one immunocompromised patients with severe cytomegalovirus (CMV) disease were treated with intravenous ganciclovir. Twenty-one patients had received transplants--15 bone marrow recipients, five renal allograft recipients, and one liver transplant recipient--while the other ten were immunocompromised due to acquired immunodeficiency syndrome (six), hematologic malignancies (three), and systemic lupus erythematosus (one). They presented with one or more of the following syndromes: CMV pneumonitis (19), CMV of the gastrointestinal tract (six), CMV retinitis (seven), and CMV hepatitis (three). Seventeen (55%) of 31 patients demonstrated clinical improvement during ganciclovir therapy, with the best response seen in the transplant recipients. Viremia ceased in 14 (93.3%) of 15 patients after a mean of 4.7 days of therapy; viruria ceased in eight (53.3%) of 15 patients after a mean of 11 days of therapy. Ganciclovir plasma concentrations at a dosage of 2.5 mg/kg/three times a day were as follows: mean peak, 16.04 mumol/L; mean trough, 2.38 mumol/L. Neutropenia occurred in 11 (35%) of 31 patients and in nine (60%) of 15 bone marrow transplant recipients. We conclude that ganciclovir exerted an antiviral effect against CMV and may play a role in the treatment of CMV disease in patients with depressed immunity, especially bone marrow and organ transplant recipients.     

更昔洛韦治疗小儿巨细胞病毒肺炎疗效观察

目的: 探讨小儿巨细胞病毒(CMV)肺炎临床特点及更昔洛韦的治疗效果。方法: 回顾性分析46例小儿CMV肺炎的临床特点,并观察30例小儿CMV肺炎更昔洛韦治疗前后临床症状、体征、肝脾大小、丙氨酸氨基转移酶(ALT)、胸片变化以及药物不良反应。结果: 小儿CMV肺炎以小婴儿发病多见,多以咳嗽为首发表现就诊(82.61%),且病程较长,有的表现为痉挛样咳。多为间质性肺炎(80.43%)。常合并有肺外表现。应用更昔洛韦5~7.5mg/kg,每12h静滴1次,治疗14天,临床症状、体征消失或明显好转,肝脾回缩,血清ALT降低,胸片吸收好转,总有效率达93.33%,未见更昔洛韦的明显副作用。结论: 对咳嗽时间较长的患儿,尤其有合并症的小婴儿应警惕CMV肺炎。更昔洛韦5~7.5mg/kg,每12h静滴1次治疗,安全、有效、副作用小。     

A case of steroid-refractory ulcerative colitis complicated with cytomegalovirus pneumonia

We present a case of late-onset ulcerative colitis (UC) complicated with cytomegalovirus (CMV) pneumonia revealed by autopsy. A 77-year-old woman had a diagnosis of UC, and received high-dose steroids and leukocytapheresis. Then she received ganciclovir because CMV-pp65 antigenemia test revealed positive which suggested systemic or colonic CMV infection. But ganciclovir was discontinued because of thrombocytopenia and liver dysfunction. After that she had interstitial pneumonia and died of a respiratory failure. Autopsy revealed CMV colitis based on UC, and CMV pneumonia with diffuse alveolar damage. Evaluation of CMV infection in patients with steroid-refractory UC should be considered before proceeding with immunosuppressive therapy or surgery, especially in elderly patients.     

Cytomegalovirus myocarditis following liver transplantation.

Cytomegalovirus (CMV) infections are commonly found in patients on immunosuppressive therapy following liver transplantation. However, acute myocarditis is an extremely rare manifestation of CMV infection in this setting. We report the case of a patient who developed acute myocarditis with severe biventricular failure with a cardiac ejection fraction of less than 10%, 6 weeks following orthotopic liver transplantation. Systemic CMV infection was diagnosed on the basis of a clinical viraemia, the presence of CMV antigen in urine, blood, and throat swab, and an associated four-fold rise in serum antibody titres to CMV. A full recovery ensued following treatment with standard anti-cardiac failure therapy and a 10 day course of intravenous ganciclovir.     

异基因造血干细胞移植后巨细胞病毒病及其危险因素分析

目的 分析异基因造血干细胞移植(Allo—HSCT)患者巨细胞病毒(CMV)病的发生及其高危因素。方法 选择自1999年8月至2001年7月在本所行Allo—HSCT患者131例,用Kaplan—Meier和Cox回归模型逐步回归方法,分析了CMV病的发生率及其相关的危险因素。结果 28例患者发生了CMV间质性肺炎(21．35％);9例发生了CMV肠炎(6．87％),CMV病的一年累积发生率为32．54％。在单因素分析中,非血缘关系供者、用抗淋巴细胞球蛋白(ALG)或抗CD3单克隆抗体、Ⅱ—Ⅳ度急性移植物抗宿主病(GVHD)、因GVHD而加用免疫抑制剂、慢性GVHD、大剂量皮质激素、输血次数、患者血浆CMV阳性均与CMV病发生率增加有关;对CMV—DNA阳性而无临床症状者进行干预性治疗使CMV—DNA阴转,则有降低CMV病发生的作用。在多因素分析时,因血浆CMV—DNA阳性、GVHD加用免疫抑制剂、大量输血使CMV病发生危险增加(RR分别为：3．309、2．242、1．046),而干预性治疗使CMV—DNA转阴降低了发病危险(RR为0．346)。13例死于CMV病。结论 CMV病是Allo—HSCT的常见并发症,也是主要致死原因之一。对血浆CMV阳性的患者进行干预性治疗至CMV转阴,可能会减少CMV病的发生。对合并Ⅱ—Ⅳ度GVHD、加用免疫抑制剂和大量输血的高危患者更有必要早期采取干预性治疗。     

肾移植术后巨细胞病毒肺炎伴急性呼吸窘迫综合征的治疗

[目的]探讨肾移植术后巨细胞病毒肺炎伴急性呼吸窘迫综合征的治疗方法。[方法]1992年至2001年我院肾移植术后巨细胞病毒肺炎合并急性呼吸窘迫综合征患者42例,全部给予呼吸机辅助呼吸、氧疗,以及抗病毒治疗,丙氧鸟苷10 mg/(kg·d),分2次静滴,7~10 d无好转加用或改用磷钾酸钠180 mg/(kg·d),分3次静滴;调整免疫抑制剂:泼尼松减量至10 mg/d,环孢素剂量减至发病前的1/3~1/4,或停用环孢素,全部停用霉酚酸酯或硫唑嘌呤,直至体温正常、症状消失;其中12例患者在此治疗基础上,给予胸腺肽(日达先)治疗,1.6 mg皮下注射,每天或隔天1次至体温正常。[结果]42例患者总存活率38％(16/42),给予胸腺肽治疗的患者存活83％(10/12),明显高于没有接受胸腺肽治疗的患者的20％(6/30)(P<0.01)。所有存活病人肾功能正常,仅1例于1个内发生急性排斥。[结论]为提高肾移植术后巨细胞病毒肺炎合并急性呼吸窘迫综合征的疗效,应给予抗病毒治疗、调整免疫抑制剂、呼吸机辅助呼吸等综合治疗;免疫增强剂胸腺肽可能提高存活率,不增加急性排斥反应的发生。     

肾移植术后感染新型冠状病毒1例

The novel coronavirus is a newly discovered pathogen in late December 2019, and its source is currently unknown, which can lead to asymptomatic infection, new coronavirus pneumonia or serious complications, such as acute respiratory failure. Corona virus disease 2019 (COVID-19) is a new type of respiratory disease that is currently spreading all over the world and caused by this coronavirus. Its common symptoms are highly similar to those of other viruses, such as fever, cough and dyspnea. There is currently no vaccine or treatment for COVID-19. Everyone is susceptible to infection with this disease, and owing to the long-term use of immunosuppressants, the immunity of kidney transplant recipients is suppressed, and it is more likely to be infected with the disease. At present, its impact on kidney transplant recipients is unclear. This article reports the clinical features and therapeutic course of novel coronavirus infection in a patient after renal transplantation. A 37-year-old female patient who received a kidney transplant 6 months before was diagnosed with novel coronavirus pneumonia. The patient’s symptoms (such as fever, chills, dry cough, muscle aches), laboratory tests (such as decreased white blood cell count, elevated liver enzymes and D-dimer, positive viral nucleic acid test), and chest CT (multiple left lower lung plaque ground glass shadow) were similar to those of non-transplanted novel coronavirus pneumonia patients. In terms of treatment, because the immunity of kidney transplant recipients has been suppressed for a long time, it is a very common strategy to suspend the use of immunosuppressive agents. Therefore, the patient immediately discontinued the immunosuppressive agent after admission, so that she could restore immunity against infection in a short time. At the same time, the use of glucocorticoids was also very important. Its immunosuppressive and anti-inflammatory effects played a large role in the treatment process.In addition, prophylactic antibiotics was needed, and nephrotoxic drugs should be used with caution. Finally, following discounting the use of immunosuppressant and a low-dose glucocorticoid-based treatment regimen, COVID-19 in this renal transplant recipient was successfully cured. The cure of this case was of great significance, and this adjuvant nonspecific antiviral therapy could provide a template for the treatment of other such patients.     

肾移植术后感染新型冠状病毒1例

The novel coronavirus is a newly discovered pathogen in late December 2019, and its source is currently unknown, which can lead to asymptomatic infection, new coronavirus pneumonia or serious complications, such as acute respiratory failure. Corona virus disease 2019 (COVID-19) is a new type of respiratory disease that is currently spreading all over the world and caused by this coronavirus. Its common symptoms are highly similar to those of other viruses, such as fever, cough and dyspnea. There is currently no vaccine or treatment for COVID-19. Everyone is susceptible to infection with this disease, and owing to the long-term use of immunosuppressants, the immunity of kidney transplant recipients is suppressed, and it is more likely to be infected with the disease. At present, its impact on kidney transplant recipients is unclear. This article reports the clinical features and therapeutic course of novel coronavirus infection in a patient after renal transplantation. A 37-year-old female patient who received a kidney transplant 6 months before was diagnosed with novel coronavirus pneumonia. The patient’s symptoms (such as fever, chills, dry cough, muscle aches), laboratory tests (such as decreased white blood cell count, elevated liver enzymes and D-dimer, positive viral nucleic acid test), and chest CT (multiple left lower lung plaque ground glass shadow) were similar to those of non-transplanted novel coronavirus pneumonia patients. In terms of treatment, because the immunity of kidney transplant recipients has been suppressed for a long time, it is a very common strategy to suspend the use of immunosuppressive agents. Therefore, the patient immediately discontinued the immunosuppressive agent after admission, so that she could restore immunity against infection in a short time. At the same time, the use of glucocorticoids was also very important. Its immunosuppressive and anti-inflammatory effects played a large role in the treatment process.In addition, prophylactic antibiotics was needed, and nephrotoxic drugs should be used with caution. Finally, following discounting the use of immunosuppressant and a low-dose glucocorticoid-based treatment regimen, COVID-19 in this renal transplant recipient was successfully cured. The cure of this case was of great significance, and this adjuvant nonspecific antiviral therapy could provide a template for the treatment of other such patients.     

成人巨细胞病毒感染54例临床分析

对５４例成人巨细胞病毒（ＣＭＶ）感染分３组进行临床分析。（１）ＣＭＶ单核细胞增多症；以发热明显而症状消遥，一过性肝功能损害，血液学改变类似传染性单核细胞增多症而ＥＢ病毒指标阴性为特征。并发症复杂但预后好。（２）ＣＭＶ肝炎：临床表现与其他病毒性肝炎相似。以急性黄疸型恢复最快，单纯转氨酶升高次之，无黄疸型较慢。单纯ＣＭＶ肝炎预后好。（３）免疫缺损者ＣＭＶ感染；７５％病例于免疫抑制治疗后发病。体温高，并发症凶险，半数病人死亡。建议对不明原因高热、肝炎、肺炎，特别是免疫缺损者，要考虑ＣＭＶ感染的可能。     

肾移植术后监测CD4+T淋巴细胞对防治巨细胞病毒肺炎的临床意义

目的 探讨监测CD4+T淋巴细胞对防治肾移植术后巨细胞病毒(cytomcgalovims,CMV)肺炎的临床意义.方法 2005年1月至2008年3月.监测133例肾移植术后受者外周血CD4'细胞计数的动态变化,根据其变化调整免疫抑制剂(Cs～Fl(506+MMF+Pred)的用量,观察调整用药对CMV肺炎发病的影响.结果 共有36例受者CD4'细胞明显下降,发生在术后45～72(61.5～9.31 d.均给予减少或停用免疫抑制剂处理.133例受者有12例出现CMV肺炎,发病在术后5耻118(76.2～11.61d.其中7例伴有急性呼吸窘迫综合征(ARDS).CD4+T细胞下降受者CMV肺炎的发病率(27.8%,10/36)明显高于CD4+细胞稳定受者(2.1%,2/97)(p,0.01),在调整用药期『日J有2例发生急性排斥反应,发生率无明显增加(P>0.05).12例CMV肺炎病人8例(66.7%,8/12)治愈.4例(33.3%,4/12)死亡.24例未发病受者在调整用药后CD4'细胞迅速上升,在14 d恢复到术前水平;8例CMV肺炎治愈者上升较缓慢,在21 d恢复;而4例死亡病人持续保持在低水平.结论 肾移植术后CD4'细胞的变化与CMV肺炎发病有密切相关性,依据其变化在CMV肺炎发病之前减少或停用免疫抑制剂是安全的,为预防和救治CMV肺炎提供一条新的方法.     

肝移植患者术后巨细胞病毒感染的危险因素分析

目的 通过分析肝移植患者住院期间的不同特征以寻找巨细胞病毒(cytomegalovirus, CMV)感染的危险因素。方法 对2016年12月至2019年2月在首都医科大学附属北京朝阳医院肝胆胰脾外科行肝移植手术并具有CMV实验室检查结果的134例患者的临床资料进行回顾性分析,其中男性113例,女性21例,平均年龄(52±10)岁。根据术后3个月内是否有CMV感染分为感染组(n=24)和对照组(n=110)。应用独立样本t检验、Mann-Whitney U秩和检验对定量资料进行单因素分析,应用卡方检验对定性资料进行单因素分析,应用Logistic回归分析进行多因素分析,探讨肝移植患者术后CMV感染的危险因素。结果 单因素分析结果显示,年龄(P=0.005)、终末期肝病模型(model for end-stage liver disease, MELD)评分(P=0.001)、Child-Pugh评分(P=0.048)、总胆红素(P=0.002)、国际标准化比值(international normalized ratio, INR)(P=0.002)、血氨(P=0.040)、腹水(P=0.042);术中术式(P=0.023)、失血量(P=0.006)、输血量(P=0.004);术后入住重症监护室(intensive care unit, ICU)时间(P=0.016)等因素是肝移植术后CMV感染的危险因素。多因素分析结果提示,MELD评分(P=0.007,95% CI:1.027~1.187)可能为肝移植术后CMV感染的独立危险因素。钙调磷酸酶抑制剂(calcineurin inhibitor, CNI)、霉酚酸酯(mycophenolate mofetil, MMF)、糖皮质激素等免疫抑制剂以及多克隆抗体的使用与肝移植患者术后早期CMV感染不相关。结论 MELD评分高可能是肝移植术后患者CMV感染的独立危险因素。免疫抑制剂不是肝移植患者术后早期CMV感染的危险因素。     

巨细胞病毒肺炎6例临床分析

目的探讨巨细胞病毒（CMV）肺炎的临床特点与诊疗措施。方法采用回顾性调查的方法对6例巨细胞病毒肺炎的临床资料进行分析。结果该组6例CMV肺炎患者均出现发热、咳嗽，伴有不同程度的呼吸困难等症状，血气分析均提示严重的缺氧，PO：明显降低；肺CT均显示双肺弥漫分布磨玻璃样阴影。更昔洛韦抗病毒，丙种球蛋白及甲强龙治疗，6例患者中3例死亡，3例存活。结论CMV肺炎常发生于恶性肿瘤大剂量化疗后、器官移植术后应用免疫抑制剂的患者，早期的诊断和及时有效的治疗是降低死亡率的关键。应停止化疗或减撤免疫抑制药物，给予有效的抗病毒治疗，对病情恶化、发生呼吸衰竭的患者应用呼吸机辅助呼吸。     

激素与免疫抑制剂治疗慢性肾病并发重症肺炎临床与CT特点

目的分析糖皮质激素（以下简称激素）与免疫抑制剂治疗慢性肾病并发重症肺炎的临床与CT特点,并总结治疗中的体会。方法回顾性分析2009年9月至2014年1月我院肾内科收治的19例接受激素与免疫抑制剂治疗的慢性肾病并发重症肺炎患者完整的临床与影像学资料,分析其致病因素、对其临床与CT特点进行总结。结果临床特点：以发热起病,多伴有寒战、乏力、胸闷、气短、轻咳、少量白痰,并迅速出现低氧血症。CT特征：早期：双肺间质性磨玻璃影为主且内见支气管血管束,少部分为散在小斑片状密度增高影;后期：双肺弥漫性磨玻璃影或大片实变影。所有患者胸腔积液无或少见,无纵膈淋巴结肿大。结论激素与免疫抑制剂治疗慢性肾病并发重症肺炎临床与CT有典型表现,CT表现结合临床可以对本病做出准确诊断。广谱抗菌药及丙种球蛋白在治疗中起了至关重要作用。     

传染性非典型肺炎腹泻的临床分析

目的分析总结传染性非典型肺炎(SARS)腹泻的临床表现及药物治疗.方法对229例SARS患者的临床资料进行回顾性分析.分为三组:A组为发病2周内发生腹泻者,B组为发病2周后发生腹泻者,C组为无腹泻发生.结果A组腹泻时CD4降低比例(72.73%)高于B组(23.08%),P＜0.05.B组(65.22%)头孢菌素使用比例高于A组(17.65%)、C组(40.22%),P＜0.05.C组抗病毒药使用比例(75.54%)高于B组(52.17%),P＜0.05.结论SARS患者在发病2周内腹泻与用药无关.发病2周后腹泻与使用头孢菌素有关.在SARS的后期,抗病毒药物能够抑制SARS病毒的复制,对防治腹泻有帮助.     

肝脏移植术后移植物抗宿主病的诊断和治疗

【目的】 探讨肝脏移植术后移植物抗宿主病（GVHD）的诊断和治疗。【方法】 分析我院2003年10月至2009年6月完成的772例肝脏移植的临床资料,总结肝脏移植术后GVHD的诊断和治疗经验。【结果】 772例肝脏移植术后5例病人发生GVHD,发病率为0.65%（5/772）,5例患者均在肝脏移植后2～5周出现发热、皮疹、腹泻和全血细胞减少,肝功能均接近正常,经皮肤活检和骨髓穿刺检查证实,并排除巨细胞病毒（CMV）和EB病毒感染。经过调整免疫抑制剂,加用IL-2受体单克隆抗体,积极抗感染和支持对症治疗,2例患者痊愈,3例患者死于严重感染、消化道出血和多器官功能衰竭。【结论】 肝脏移植术后GVHD死亡率高,早期诊断,及时调整免疫抑制剂方案,积极抗感染和营养支持是治疗的关键。     

抗原血症检测方法早期诊断白血病患儿的巨细胞病毒性肺炎

目的：了解白血病患儿巨细胞病毒（ＣＭＶ）肺炎的发生状况及ＣＭＶ抗原血症检测方法对ＣＭＶ肺炎的诊断意义。方法：实验组为３１例白血病患儿，对照组为３１例免疫功能正常的儿童，应用间接免疫荧光方法检测外周血白细胞ＣＭＶ抗原；应用ＥＬＩＳＡ方法检测血清抗ＣＭＶＩｇＭ、ＩｇＧ抗体。结果：白血病患儿中有９例发生活动性ＣＭＶ感染，感染率为２９１％，对照组为０，两者之间差异显著（Ｐ＜００１）。９例活动性ＣＭＶ感染患儿中，有６例为肺炎，临床表现无特异性，胸片表现多样化，病情轻重不一。６例ＣＭＶ肺炎患儿检测ＣＭＶ抗原血症均为阳性。结论：白血病患儿易发生ＣＭＶ肺炎。ＣＭＶ抗原血症检测技术可早期诊断白血病患儿ＣＭＶ肺炎，为临床早期治疗提供实验依据     

成人肝移植术后肺部并发症回顾分析

目的探讨成人肝移植术后早期(3个月内)肺部并发症的种类、发生率及原因。方法回顾性分析49例肝移植术后与肺部并发症(胸腔积液、肺部感染、肺水肿、肺不张和急性呼吸功能衰竭)发生可能的相关因素。结果在肝移植术后早期有34例患者合并肺部并发症,发生率为69．4％。最常见为胸腔积液(n=26,53．1％),其后依次为肺部感染(n=8,16．3％)、肺不张(n=6,12．3％)、急性呼吸功能衰竭(n=5,10．2％)、肺水肿(n=2,4．1％)。与未发生肺部并发症的病例相比,发生者组的死亡率明显偏高(P=0．048),术后拔除气管插管的时间明显延长(P=0．042),术后第1天的凝血功能较差(P=0．023)。并发胸腔积液的患者仅3例需行引流术,其他均自愈。结论采取有效措施减少危险因素,早期诊断及治疗肝移植术后的早期肺部并发症对提高肝移植患者的预后是极为重要的。     

异基因干细胞移植后间质性肺炎的预防和治疗

目的探讨异基因造血干细胞移植中巨细胞病毒（CMV）感染和间质性肺炎（IP）的预防和治疗。方法2002年9月至2005年9月对24例患者进行异基因造血干细胞移植，男14例，女10例，其中12例接受清髓性、12例接受非清髓性预处理方案移植。用膦甲酸钠联合阿昔洛韦预防CMV感染和IP，对已发生CMV感染或IP的患者，将阿昔洛韦改为更昔洛韦治疗。结果移植后有4例（16．7％）感染CMV，中位时间为移植后49d，经治疗后好转；有3例（12．5％）发生IP，其中2例CMV—DNA在正常范围，1例患者为巨细胞病毒间质性肺炎（CMV—IP）。经治疗后，3例IP1例死亡，2例好转。结论膦甲酸钠联合阿昔洛韦或更昔洛韦预防治疗IP效果良好。     

肾移植术后早期环孢菌素A引起的肝损害

目的探讨肾移植术后3个月CsA免疫抑制剂的肝损害治疗措施.方法对19例出现肝功能异常的病例进行分析,测定肝功能异常时CsA的谷值浓度.及时调节免疫抑制剂用量,配合保肝利胆治疗.结果17例于2～4周肝功能恢复正常.2例无效,将CsA改为FK506后1个月后,肝功能指标逐渐恢复正常.结论低剂量CsA、MMF、pred三联是目前理想的免疫抑制治疗方案,结合保肝治疗,对减少术后早期CsA肝毒性的发生有一定疗效.     

异基因造血干细胞移植后巨细胞病毒肺炎临床特点分析

目的：研究定量监测血浆巨细胞病毒(cytomegalovirus,CMV)DNA水平指导的抗病毒抢先治疗下, 造血干细胞移植后CMV肺炎的临床特点及预后。方法:分析2005年1月至2008年8月之间行异基因造血干细胞移植(allogeneic hematopoietic stem-cell transplantation, allo-HSCT)后发生CMV肺炎的22例患者, 总结发病的临床特征及评价影响预后的相关因素。结果:750例allo-HSCT患者中共22例发生24例次CMV肺炎(2.9%), 发病中位时间为+51d(+30～180 d), 16例(72.7%)患者在发病前后出现CMV血症, 6例患者血浆CMV-PCR持续阴性。23例次患者胸部CT上出现间质性改变(如弥漫的磨玻璃影、多发斑片影等)。治疗上抗病毒药物联合皮质激素疗效较好, CMV肺炎总体治愈率为83.3%。单因素分析发现男性患者及重度急性移植物抗宿主病(acute graft-versus-host disease, aGVHD)是CMV肺炎的不良预后因素(P=0.034, P=0.023)。结论: 通过定量PCR监测CMV-DNA水平, 尽早诊断并给予适当抗病毒治疗可以明显改善CMV肺炎患者的预后。