先天性巨细胞病毒感染抗病毒治疗的效果和安全性观察

摘要

目的 观察更昔洛韦(GCV)和(或)缬更昔洛韦(VGCV)治疗先天性巨细胞病毒(CMV)感染患儿的疗效和不良反应.方法 回顾性纳入2012年3月1日至2017年5月31日在复旦大学附属儿科医院(我院)新生儿科住院、确诊为先天性CMV感染的患儿,随访至2017年12月31日.从病史资料中提取患儿的一般资料,抗CMV治疗的药物和疗程,新生儿期及1、3和6月龄的肝脾触诊检查结果、胆红素和肝功能检查指标、CMV抗体和DNA检测结果、颅脑MRI、眼底检查结果和听力检测结果,治疗期间药物的不良反应.根据抗病毒治疗与否以及疗程长短分组,比较各组的临床特征和治疗反应.结果 28例先天性CMV感染患儿进入本文分析,其中早产儿11例,男17例;无症状/轻度症状9例,未予抗病毒治疗;中重度症状19例,GCV和(或)VGCV治疗≤6周组11例,治疗6个月组8例.①6月龄时,除1例胆汁酸轻度升高外27例中枢神经系统以外的症状和体征、胆红素、肝功能和血常规均恢复正常.②无症状/轻度症状组1例在6月龄时出现左侧听力中度损失.治疗≤6周组中,2例CMV相关眼底病变于1月龄时消失;颅脑MRI异常信号和听力损失者各5例,6月龄时分别有3例和2例无改善.治疗6个月组中,4例先天性CMV感染相关视网膜病变在随访中均消失;3例头颅MRI异常信号者和7例有听力损失者,6月龄时分别有2例和1例无改善.③治疗≤6周组和治疗6个月组在6月龄时中枢神经系统病变改善情况差异无统计学意义.④治疗过程中未发现与GCV和VGCV应用相关的粒细胞减少和肝功能异常.结论 抗病毒治疗能改善感音神经性耳聋和脉络膜视网膜炎,GCV和(或)VGCV≤6周与6个月的治疗效果相近;建议对无临床症状先天性CMV感染患儿行眼底检查、脑干诱发电位和头颅MRI检查.%Objective To evaluate the effect and side effect of the antiviral regimens consisting of ganciclovir and/or valganciclovir on congenital cytomegalovirus (CMV) infected neonates.Methods Retrospective analyze the data of neonates with congenital CMV infection hospitalized in the Newborn Department of the Children's Hospital of Fudan University from March 2012 to May 2017.The clinical characteristics,liver function,CMV DNA,brain MRI,fundus examination and treatment results of 3 groups were evaluated and compared.Results Twenty-eight neonates were diagnosed as congenital CMV infection.Of whom,nine were asymptomatic or with mild symptoms and had not been treated with antiviral therapy;the remaining nineteen cases were congenital CMV infection with moderate or severe symptoms;among them,eleven cases were treated with ganciclovir and/or valganciclovir ≤6 weeks;and eight cases were treated with ganciclovir and/or valganciclovir for 6 months.① When followed up to 6 months old,except 1 patient had moderate elevated bile acid,all the other 27 had recovered symptoms and signs except the central nervous system,liver function and blood routine examination.② In neonates with asymptomatic congenital CMV infection or with mild symptoms,a left hearing loss case emerged at 6 month.In ≤ 6 weeks antiviral group,2 CMV-related fundus lesions healed in 1 month old;3/5 patients still had abnormal brain MRI image and 2/5 patients had hearing loss when 6 months old.In 6 months treated group,all 4 fundus lesionsrelated to congenital CMV infection healed at the end of 6 months follow up,while 2/3 case still had abnormal brain MRI image and 1/7 with hearing loss.③ No statistical difference was observed in central nervous system symptom between 6 weeks group and 6 months group.④ No ganciclovir and/or valganciclovir related granulocytopenia and liver dysfunction occurred during follow-up.Conclusion Treatments with ganciclovir and/or valganciclovir for ≤ 6 weeks or 6 months could improve senorineural hearing loss and chorioretinitis;while no significant difference regarding improvement of these lesions were observed between ≤ 6 weeks and 6-months treated groups at 6 month old.It is suggested that,neonates with asymptomatic congenital CMV infection should be screened by ophthalmoscopic examination,auditory brainstem response and MRI,early active antiviral therapy is recommended for neonate with emerging symptom.