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肝移植术后巨细胞病毒感染:预防与抢先治疗——单中心经验

Cytomegalovirus infection after liver transplantation: prophylaxis and preemptive treatment--a single-center experience.

作者信息

Perrella A, Esposito C, Ioia G, Campanella L, Taglialatela D, Cuomo O

机构信息

Liver Transplant Center, Naples, Italy.

出版信息

Transplant Proc. 2010 May;42(4):1226-8. doi: 10.1016/j.transproceed.2010.03.060.

DOI:10.1016/j.transproceed.2010.03.060
PMID:20534267
Abstract

BACKGROUND

Cytomegalovirus (CMV) infection represents one of the most frequent opportunistic infections following solid-organ transplantation. The incidence and severity of CMV infection depend on the immunosuppressive regimen, the CMV serostatus of donor and recipient, and the type of transplant.

METHODS

We evaluated CMV infection rates during the last 2 years in our center: March 2007 to March 2009. We enrolled 55 patients-13 females and 42 males-who underwent liver transplantation (OLT) due to hepatitis C virus (HCV) cirrhosis (n = 9), hepatitis B virus (HBV) cirrhosis (n = 5) HCC both on HCV and HBV cirrhosis (n = 37), or autoimmune disease (n = 4). Fifty percent of the patients received tacrolimus (TRL) and the others cyclosporine (CsA), both dosed according to weight. All patients received oral acyclovir (400 mg/td or less, adapted to renal function) as herpes simplex prophylaxis for 6 months. CMV prophylaxis prescribed CMV- hyperimmunoglobulin on postoperative days 1 and 7. CMV infection was monitored using polymerase chain reaction (PCR <1000 IU/mL) according to the following schedule: every week for the first month, every 2 weeks from month 2 to 3 and monthly from month 4 to 6. Patients were treated when three positive PCR results not affected by immunosuppressive dose reduction or when the PCR showed DNA greater than three times the limit of detection. CMV treatment stipulated valgancyclovir (900 mg twice daily) until three consecutive PCRs were negative or for 3 months dosed according to renal function. PCR was measured every 2 weeks during treatment.

RESULTS

Among the patients who were all D(+)/R(+) (CMV-Immunoglobulin G IgG/IgG(+)). 10 required treatment (18%) within 3 months from OLT. There subjects were prescribed TRL (n = 4) or CsA (n = 6). No renal impairment was observed among treated patients. Of those having the infection, one died due to other causes-sepsis from candida at 5 months after OLT.

CONCLUSION

CMV-hyperimmunoglobulin on postoperative days 1 and 7 did not confer protection for CMV among OLT patients. Preemptive treatment with intravenous gancyclovir plus valgancyclovir per os seemed to be useful and safe in infected patients requiring treatment.

摘要

背景

巨细胞病毒(CMV)感染是实体器官移植后最常见的机会性感染之一。CMV感染的发生率和严重程度取决于免疫抑制方案、供体和受体的CMV血清学状态以及移植类型。

方法

我们评估了本中心过去两年(2007年3月至2009年3月)的CMV感染率。我们纳入了55例患者,其中13例女性和42例男性,他们因丙型肝炎病毒(HCV)肝硬化(n = 9)、乙型肝炎病毒(HBV)肝硬化(n = 5)、HCV和HBV肝硬化合并肝癌(n = 37)或自身免疫性疾病(n = 4)接受了肝移植(OLT)。50%的患者接受他克莫司(TRL),其余患者接受环孢素(CsA),两者均根据体重给药。所有患者接受口服阿昔洛韦(400mg/天或更少,根据肾功能调整)作为单纯疱疹预防用药,为期6个月。CMV预防方案为在术后第1天和第7天给予CMV高免疫球蛋白。根据以下时间表,使用聚合酶链反应(PCR<1000IU/mL)监测CMV感染:第1个月每周一次,第2至3个月每2周一次,第4至6个月每月一次。当三次PCR结果为阳性且不受免疫抑制剂量减少影响,或PCR显示DNA大于检测限的三倍时,对患者进行治疗。CMV治疗规定使用缬更昔洛韦(900mg,每日两次),直到连续三次PCR结果为阴性或根据肾功能给药3个月。治疗期间每2周测量一次PCR。

结果

在所有患者均为D(+)/R(+)(CMV免疫球蛋白G [IgG](+)/IgG(+))的患者中,10例(18%)在OLT后3个月内需要治疗。这些患者中,4例接受TRL治疗,6例接受CsA治疗。治疗患者中未观察到肾功能损害。在感染患者中,1例因其他原因死亡——OLT后5个月因念珠菌败血症死亡。

结论

术后第1天和第7天给予CMV高免疫球蛋白对OLT患者的CMV没有保护作用。对于需要治疗的感染患者,静脉注射更昔洛韦加口服缬更昔洛韦的抢先治疗似乎是有用且安全的。

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