Citrin缺陷导致新生儿肝内胆汁淤积症的临床特征及中药利胆合剂治疗效果观察

Clinical features of neonatal intra-hepatic cholestasis caused by citrin defects and observation on therapeutic effect of Linda mixture for treatment of the disease

目的观察用病证结合模式自主研发的中药利胆合剂方治疗新生儿肝内胆汁淤积症（NICCD）的临床疗效，为早期诊治NICCD提供经验。方法回顾性分析2012年6月至2015年6月武汉市儿童医院中西结合科住院期间通过NICCD常见基因位点检测确诊的20例Citrin缺陷导致的NICCD患儿的临床特征。观察中药利胆合剂治疗NICCD的临床疗效，以及治疗前后肝功能及凝血功能指标的变化，彩色超声测定患儿治疗前后的肝脾肿大情况。结果20例患儿均以3个月内病理性黄疸起病，经治疗临床痊愈15例，好转5例，平均住院时间（14．67±1．56）d。治疗后血清总胆红素（TBil）、直接胆红素（DBil）、丙氨酸转氨酶（ALT）、胆汁酸（TBA）水平均较治疗前均明显降低[TBil（μmol／L）：64．0±39．5比173．5±54．1，DBil（μmol／L）：37．7±24．8比80．9＋46．4，ALT（U／L）：42．1±25．8比55．0±32．2，TBA（μmol／L）：67．5±203比195．0±61．3，均P〈0．05]，白蛋白（Alb）、总蛋白（GLB）均较治疗前明显升高[Alb（U／L）：37．9±4．7比33．1±4．7，GLB（g／L）：17．3±4．0比14．6±2．8，均P〈0．05]，凝血功能指标活化部分凝血活酶时间（APTT）较治疗前明显缩短（S：38．2±8．3比63．1±24．0，P〈0．05）。彩色超声显示：治疗后肝脾肿大较治疗前明显缩小[肝脏肿大（cm）：2．12±0．70比3．04-4-0．25，脾脏肿大（cm）：0．25±0．03比0．58±0．32，均P〈0．05]。1个月后回访患儿体质量基本在正常范围，平均增长（1．01±0．32）kg，大便颜色较入院时明显改善，大便次数较人院时减少，15例患儿大便金黄色，5例大便浅黄，无陶土色大便。18例患儿大便次数保持在5次以下，脂肪泻的状况明显好转。结论中药治疗NICCD可取得明显的临床疗效。

Objective To observe the clinical efficacy of Linda mixture self made by combination of disease with syndrome pattern for treatment of neonatal intrahepatic cholestasis disease caused by Citrin defects （NICCD） and to provide an experience in early diagnosis and treatment of NICCD. Methods The clinical features of 20 patients with NICCD was confirmed by NICCD common genetic loci detection during hospitalization admitted to the Department of Integrated Traditional and Western Medicine in Wuhan Children Hospital from June 2012 to June 2015 were retrospectively analysed. The clinical efficacy of Chinese medicine Linda mixture for treatment of NICCD, before and after treatment, the index changes of liver function and coagulation function were observed and Color Doppler ultrasound was used to detect the situation of hepatosplenomegaly in the patients. Results There were 20 cases all their pathological jaundice occurring within 3 months old, after treatment, 15 eases of them obtained clinical recovery and 5 cases were getting better, the average length of stay in hospital was （14.67 ± 1.56） days. After the treatment, the levels of serum total bilirubin （TBil）, direct bilirubin （DBil）, alanine aminotransferase （ALT）, total bile acid （TBA） were markedly lower compared with those before treatment [TBil （μmol/L）： 64.0 ± 39.5 vs. 173.5 ±54.1, DBil （μmol/L）： 37.7±4.8 vs. 80.9±46.4, ALT （U/L）： 42.1±25.8 vs. 55.0±32.2, TBA （μmol/L）： 67.5±20.3 vs. 195.0±61.3, all P 〈 0.05], albumin （Alb） and total albumin （GLB） were significantly higher compared with those before treatment [Alb （U/L）： 37.9 ±4.7 vs. 33.1± 4.7, GLB （g/L）： 17.3 ± 4.0 vs. 14.6 ± 2.8, both P 〈 0.05], activated partial thromboplastin time （APTT） of coagulation function was significantly reduced （s： 38.2±8.3 vs. 63.1± 24.0, P 〈 0.05）. Color Doppler ultrasound examination showed that hepatosplenomegaly was shrunk after treatment [hepatomegaly （cm）： 2.12-4-0.70 vs. 3.04 ± 0.25, splenomegaly （cm）： 0.25±0.03 vs. 0.58±0.32, both P 〈 0.05]. After 1 month of follow up, the infants＇ body weights were almost normal, the average increase in weight being （1.01 ± 0.32） kg, the color and frequency of stool were distinctly better compared with those before treatment, the stool color in 15 cases was golden, pale yellow in 5 cases andno one, pottery clay in color. The stool frequeneies of 18 cases were kept under 5 times, and fatty diarrhea situation was ameliorated. Conclusion Using Chinese medicine for treatment of NICCD can obtain significant clinical effects.