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缬更昔洛韦预防后成年肝移植(D+/R-)患者原发性巨细胞病毒感染的前瞻性长期研究。

Prospective long-term study on primary CMV infections in adult liver transplant (D+/R-) patients after valganciclovir prophylaxis.

作者信息

Lautenschlager Irmeli, Loginov Raisa, Mäkisalo Heikki, Höckerstedt Krister

机构信息

Department of Virology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Department of Virology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

出版信息

J Clin Virol. 2015 Oct;71:73-5. doi: 10.1016/j.jcv.2015.08.009. Epub 2015 Aug 20.

DOI:10.1016/j.jcv.2015.08.009
PMID:26318605
Abstract

BACKGROUND

Cytomegalovirus (CMV) can cause severe infections in transplanted patients. To prevent CMV infection, most liver centers use prophylaxis for CMV-seronegative recipients receiving an organ from a seropositive donor (D+/R-). Valganciclovir is mostly given for 3-6 months after transplantation. However, the patients may develop primary CMV infection after the cessation of prophylaxis and late-onset CMV disease may occur.

OBJECTIVES

A prospective long-term follow-up of CMV (D+/R-) adult liver transplant recipients after 3 months valganciclovir prophylaxis was investigated.

STUDY DESIGN

Of 154 consecutive adult liver recipients transplanted from 2006 to 2009, 20 (13%) were CMV D+/R- and received antiviral prophylaxis up to 3 months after transplantation. After excluding the recipients with incomplete prophylaxis or monitoring, 13 (D+/R-) patients with follow-up of >4 years after the 3-month period of valganciclovir prophylaxis were included in the study.The patients were monitored for CMV by real-time quantitative plasma PCR.

RESULTS

No break-through CMV infections were recorded during the prophylaxis period. After cessation of valganciclovir prophylaxis 12/13 (90%) patients demonstrated CMV-DNAemia following a post transplantation mean interval of 165 days (range 95-320). Ten patients with high viral loads (peak viral load mean 81,510, range 1900-648950cps/ml) were successfully treated, 6 with valganciclovir, and 4 with ganciclovir. Two patients with low level CMV-DNAemia (<1000cps/ml) were asymptomatic and not treated. No intragraft infection was seen, but one patient developed gastrointestinal CMV infection verified from ileum biopsy. During long-term follow-up, 3 patients demonstrated low-level viral replication, but no symptomatic recurrences occurred. One patient died of bacterial sepsis, but no patient or graft was lost due to CMV.

CONCLUSIONS

Primary CMV infections after cessation of prophylaxis were common, but were successfully treated with valganciclovir or ganciclovir.

摘要

背景

巨细胞病毒(CMV)可在移植患者中引起严重感染。为预防CMV感染,大多数肝脏中心对接受血清学阳性供体器官的血清学阴性受体(D+/R-)进行预防。缬更昔洛韦大多在移植后给予3至6个月。然而,患者在预防措施停止后可能发生原发性CMV感染,并可能出现迟发性CMV疾病。

目的

对接受缬更昔洛韦预防3个月后的CMV(D+/R-)成年肝移植受者进行前瞻性长期随访研究。

研究设计

在2006年至2009年连续接受肝移植的154例成年受者中,20例(13%)为CMV D+/R-,并在移植后接受了长达3个月的抗病毒预防。在排除预防或监测不完整的受者后,13例(D+/R-)在缬更昔洛韦预防3个月后随访超过4年的患者被纳入研究。通过实时定量血浆PCR对患者进行CMV监测。

结果

在预防期间未记录到突破性CMV感染。缬更昔洛韦预防停止后,12/13(90%)的患者在移植后平均165天(范围95 - 320天)出现CMV血症。10例病毒载量高的患者(峰值病毒载量平均81,510,范围1900 - 648950cps/ml)得到成功治疗,6例用缬更昔洛韦治疗,4例用更昔洛韦治疗。2例CMV血症水平低(<1000cps/ml)的患者无症状,未接受治疗。未观察到移植内感染,但1例患者经回肠活检证实发生胃肠道CMV感染。在长期随访中,3例患者出现低水平病毒复制,但未出现症状复发。1例患者死于细菌性败血症,但没有患者或移植物因CMV而丢失。

结论

预防措施停止后的原发性CMV感染很常见,但用缬更昔洛韦或更昔洛韦可成功治疗。

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