二巯丁二酸联合硫酸锌与青霉胺治疗儿童肝豆状核变性的效果比较  

Effect of dimercaptosuccinic acid combined with zinc sulfate versus D-penicillamine in treatment of children with Wilson’s disease

作　　者：田雪 徐志强 董漪 闫建国 曹丽丽 冯丹妮 高银杰 许世友 毕京峰 王福川 张敏[1,2] TIAN Xue;XU Zhiqiang;DONG Yi;YAN Jianguo;CAO Lili;FENG Danni;GAO Yinjie;XU Shiyou;BI Jingfeng;WANG Fuchuan;ZHANG Min(The Second Medical School of Southern Medical University,Guangzhou 510000,China;Department of Hepatology,The Fifth Medical Center of Chinese PLA General Hospital,Beijing 100000,China;Department of Pediatrics,Minle Maternal and Child Health Hospital,Zhangye,Gansu 734000,China)

机构地区：[1]南方医科大学第二临床学院,广州510000 [2]解放军总医院第五医学中心肝病科,北京100000 [3]民乐县妇幼保健院儿科,甘肃张掖734000

出　　处：《临床肝胆病杂志》2023年第9期2145-2150,共6页Journal of Clinical Hepatology

基　　金：首都特色课题(Z181100001718030);首都医学发展基金(2022-1-2182)。

摘　　要：目的比较二巯丁二酸联合硫酸锌与青霉胺单药治疗儿童肝豆状核变性12个月的疗效,为临床用药提供参考。方法纳入解放军总医院第五医学中心2018年5月—2021年5月住院治疗的111例2~18岁肝豆状核变性患儿,随机分配至二巯丁二酸联合硫酸锌治疗组(联合组,n=52)和青霉胺单药治疗组(单药组,n=59),比较两组患儿基线、治疗6个月及12个月时的肝功能实验室指标和24 h尿铜。计量资料两组间比较采用Mann-Whitney U检验,组内比较采用Wilcoxon符号秩和检验。计数资料两组间比较采用χ^(2)检验或Fisher检验。结果治疗12个月时,联合组因药物不良反应脱落率为3.85%(2/52),低于单药组脱落率20.34%(12/59),差异有统计学意义(χ^(2)=6.821,P=0.009)。治疗6个月和12个月时,联合组及单药组患儿肝功能ALT、AST水平均改善,与治疗前相比差异均有统计学意义(P值均<0.001),而治疗后两组间比较差异均无统计学意义(P值均>0.05)。治疗6个月时两组患儿24 h尿铜水平上升,12个月时下降,两组患儿分别下降至123.00(80.25~204.04)μg/24 h、239.50(171.50~490.25)μg/24 h,单药组24 h尿铜水平显著高于联合组(Z=-3.090,P=0.002)。治疗12个月时两组肝硬度值(LSM)≥7.3 kPa的患儿LSM均有下降,联合组患儿(n=22)LSM下降了1.8(0.3~7.2)kPa,单药组(n=13)患儿LSM下降了2.2(0.9~7.0)kPa,两组的LSM下降人数占比分别为81.82%、84.62%,差异无统计学意义(χ^(2)=0.127,P=0.721)。结论二巯丁二酸联合硫酸锌方案对比青霉胺单药方案治疗儿童肝豆状核变性,尽管尿排铜量低,但二者在临床疗效方面无显著性差异,且前者安全性优于后者。Objective To investigate the effect of dimercaptosuccinic acid(DMSA)combined with zinc sulfate versus Dpenicillamine(DPA)monotherapy in the treatment of children with Wilson’s Disease(WD),and to provide a reference for clinical medication.Methods A total of 111 children with WD,aged 2-18 years,who were admitted to the Fifth Medical Center of Chinese PLA General Hospital from May 2018 to May 2021 were enrolled in this study and were randomly divided into DMSA+zinc sulfate treatment group(combination group with 52 children)and DPA monotherapy group(monotherapy group with 59 children),and the two groups were compared in terms of liver function parameters and 24-hour urinary copper at baseline and 6 and 12 months of treatment.The Mann-Whitney U test was used for comparison of continuous data between two groups,and the Wilson rank sum test was used for comparison within each group;the chi-square test or the Fisher’s test was used for comparison of categorical data between two groups.Results At 12 months of treatment,the combination group had a significantly lower loss to follow-up rate due to adverse drug reactions than the monotherapy group[3.85%(2/52)vs 20.34%(12/59),χ^(2)=6.821,P=0.009].At 6 and 12 months of treatment,both the combination group and the monotherapy group had significant improvements in alanine aminotransferase and aspartate aminotransferase(all P<0.001),while there were no significant differences between the two groups after treatment(all P>0.05).Both groups had an increase in 24-hour urinary copper at 6 months of treatment and a reduction at 12 months of treatment,with a level of 123.00(80.25-204.04)μg/24 h in the combination group and 239.50(171.50-490.25)μg/24 h in the monotherapy group,and the monotherapy group had a significantly higher level of 24-hour urinary copper than the combination group(Z=-3.090,P=0.002).For both groups at 12 months of treatment,there was a reduction in LSM in the children with a liver stiffness measurement(LSM)of≥7.3 kPa;LSM was reduced by 1.8(0.3-7.2)kPa in t

关 键 词：肝豆状核变性 二巯琥珀酸 硫酸锌 青霉胺 治疗结果 

分 类 号：R742.4[医药卫生—神经病学与精神病学]