Risk factors associated with mortality in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and clinical implications
Risk factors associated with mortality in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and clinical implications
复制标题
柑橘缺乏引起的新生儿肝内胆汁淤积症 (NICCD) 死亡的相关危险因素及临床意义
DOI：
10.1186/s12887-018-1383-5
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发表时间：
2019-01-14
期刊：
影响因子：
2.4
通讯作者：
Wang, Jian-She
中科院分区：
文献类型：
--
作者：
Abuduxikuer, Kuerbanjiang;Chen, Rui;Wang, Jian-She
Citrin缺乏引起的新生儿肝内胆汁淤积症（NICCD）在东亚地区有较高的患病率，在世界其他地区也有报道。NICCD也是东亚人中最常见的遗传性胆汁淤积症。有死亡或肝移植与NICCD相关的报道，但与不良结局相关的风险因素尚不清楚。我们的目的是报告NICCD死亡率在三级儿科肝病中心，并探讨相关的危险因素沿着与临床practice.MethodThis是一个回顾性分析NICCD病例收集从2003年6月至2017年1月在复旦大学附属儿童医院。临床，生化和遗传数据进行了比较死者的情况下，幸存者没有肝transplant.Results61确认NICCD的情况下，包括52例生存组，9例死亡组，被列入分析。死亡组转诊时的平均年龄显著高于存活组（9.58 ± 5.03 VS 3.96 ± 3.13个月，p< 0.000）。死亡组中感染的比例显著高于存活组（p= 0.023）。死亡组中44.4%的患者未接受无乳糖和/或富含中链甘油三酯（LF/MCT）的配方奶粉，这一比例显著高于存活组（9.6%，p = 0.021）。死亡组的平均血小板（PLT）计数显著低于存活组（p= 0.010）。死亡组的平均血清γ-谷氨酰转肽酶（GGT）和总胆固醇（TCH）水平显著低于存活组，p值分别为0.001和0.019。死亡者的血清铵水平高于幸存者（p= 0.016）。死亡组的瓜氨酸平均水平显著低于存活组（p= 0.010）。另一方面，酪氨酸的平均水平显着高于死亡率组的生存组（P= 0.015）。结论晚期转诊，感染的存在，延迟治疗LF/MCT公式，血小板计数降低，GGT水平降低，总胆固醇，血瓜氨酸，血氨和酪氨酸水平较高，与预后不良NICCD。
BackgroundNeonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) has high prevalence in East Asia, and has been reported in other parts of the world. NICCD is also the most common form of genetic cholestasis among East Asians. There has been reports of mortalities or liver transplants associated with NICCD, but risk factors associated with poor outcome were unknown. Our objective is to report NICCD mortalities in a tertiary pediatric hepatology center, and to explore associated risk factors along with implications to clinical practice.MethodThis is a retrospective analysis of NICCD cases collected from June 2003 until January 2017 in the Children’s Hospital of Fudan University. Clinical, biochemical, and genetic data were compared between deceased cases and survivors without liver transplant.ResultsSixty-one confirmed NICCD cases, including 52 cases in the survival group, and 9 cases in the mortality group, were included in the analysis. Mean age at referral in the mortality group was significantly higher when compared to the survival group (9.58 ± 5.03 VS 3.96 ± 3.13 months,p< 0.000). The proportion with infection in the mortality group was significantly higher than the survival group (p= 0.023). 44.4% of patients in the mortality group did not receive lactose-free and/or medium chain triglycerides enriched (LF/MCT) formula, and this percentage was significantly higher than the survival group (9.6%,p= 0.021). Mean platelet (PLT) count in the mortality group was significantly lower than the survival group (p= 0.010). Mean serum gamma-glutamyl transpeptidase (GGT), and total cholesterol (TCH) levels were significantly lower in the mortality group when compared to the survival group withpvalues of 0.001, and 0.019, respectively. Those who died had higher serum ammonium levels than survivors (p= 0.016). Mean level of citrulline was significantly lower in the mortality group compared to the survival group (p= 0.010). On the other hand, mean level of tyrosine was significantly higher in the mortality group than that of the survival group (p= 0.015).ConclusionLate referral, presence of infection, delayed treatment with LF/MCT formula, lower platelet count, lower levels of GGT, total cholesterol, blood citrulline, and higher level of blood ammonia and tyrosine, were associated with poor prognosis in NICCD.