更昔洛韦治疗对Connexin26基因突变巨细胞病毒感染婴儿听力的影响

目的 研究更昔洛韦治疗对Connexin26基因突变的巨细胞病毒感染婴儿听力的影响,并了解是否可以逆转此类婴儿的听力损害情况。 方法 从温州医科大学附属第二医院及金华永康市第一人民医院筛选血和尿液CMV-DNA阳性婴儿，根据人Connexin26基因编码区核苷酸全序列，进行RT-PCR检测，获得产物继续碱基测序，存在基因突变的巨细胞病毒感染婴儿70例作为研究对象。根据血生化结果，将肝功能损害的婴儿列为Ⅰ组(22例，进行更昔洛韦治疗)，将无肝功能损害的婴儿随机分为更昔洛韦治疗组(Ⅱ组，24例)和非更昔洛韦治疗组(Ⅲ组，24例)，更昔洛韦的治疗为诱导期剂量为每次5 mg/kg，每12 h一次，持续14 d，此后改为1次/d维持治疗，剂量同前，持续7 d,复查肝功能及CMV-DNA拷贝数，检测并追踪患儿治疗前后脑干听觉诱发电位变化，比较各组肝功能指标、CMV-DNA拷贝数及脑干诱发电位结果。 结果 经过更昔洛韦治疗，Ⅰ组婴儿肝功能异常情况明显好转(ALT:t=8.610 9,P＜0.000 1；AST:t=15.007 7,P＜0.000 1；TBil:t=10.993 3,P＜0.0001)，Ⅰ组和Ⅱ组CMV-DNA拷贝数明显下降(t=5.460 4,P＜0.000 1)，但BAEP检测异常的婴儿听力损害情况没有好转，部分患儿呈恶化趋势，而Ⅲ组婴儿听力损害情况无明显变化。 结论 更昔洛韦治疗对巨细胞病毒感染所致肝炎等炎症性疾病有效，但对感音性神经性聋，特别是有Connexin26基因突变的听力损害无效。 

Effect of ganciclovir on improving listening comprehension in infants with cytomegalovirus infection and Connexin 26 gene mutation

Objective To study on the effect of ganciclovir on the hearing in the infants with cytomegalovirus(CMV) infection and Connexin 26 gene mutations,and its role in improving the hearing impairment of such infants. Methods The infants with positive CMV-DNA in blood and urine were screened.RT-PCR and DNA sequencing were performed and Connexin 26 gene mutations were found in 70 infants.22 infants with hepatic injury were assigned into Group Ⅰ(22 cases,receiving ganciclovir treatment),while 48 infants without liver function damage were divided into ganciclovir treatment group(Group Ⅱ,24 cases) and non ganciclovir treatment group (Group Ⅲ,24 cases).The treatment induced the induction dose of 5 mg/kg Ganciclovir,q12h,continuous 14 days,and then changed to QD maintenance therapy with same dose,continuous 7 days.The liver function index and CMV-DNA copy number were re-detected.The changes of brainstem auditory evoked potential were tracked.The liver function,CMV-DNA copy number and brain stem evoked potential between the two groups were compared. Results After ganciclovir treatment,the liver function in Group Ⅰ was improved obviously(ALT:t=8.610 9,P<0.000 1,AST:t=15.007 7,P<0.000 1,TBil:t=10.993 3,P<0.000 1),CMV-DNA copy number in both Group Ⅰ and Group Ⅱ decreased significantly(t=5.460 4,P<0.000 1),but the hearing impairment by BAEP was improved,even worse in some children,while the infant hearing impairment in Group Ⅲ had no significant deterioration. Conclusion Ganciclovir treatment is effective on the hepatitis caused by cytomegalovirus infection and other inflammatory diseases,but cannot improve the sensorineural hearing loss(neurosensory deafness),especially the hearing impairment associated with Connexin 26 gene mutation in infants.