Pediatric Intestinal Failure-Associated Liver Disease: Challenges in Identifying Clinically Relevant Biomarkers
Pediatric Intestinal Failure-Associated Liver Disease: Challenges in Identifying Clinically Relevant Biomarkers
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DOI：
10.1177/0148607116671781
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发表时间：
2018-02-01
影响因子：
3.4
通讯作者：
Puder, Mark
中科院分区：
文献类型：
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作者：
Gura, Kathleen M.;Mulberg, Andrew E.;Puder, Mark
背景资料：肠衰竭相关肝病（IFALD）是一种复杂的疾病，通过同时使用肠外营养、临床表现和肝脏生物标志物的改变（不包括其他肝病原因）进行诊断。与单个指标相比，复合生物标志物可能提供比单个参数更有效的评估疾病进展和治疗反应的方法。由于IFALD被一些人认为是一种药物性肝损伤（DILI），因此这些诊断标准可能适用于该人群。使用IFALD治疗儿童的现有数据库，我们的目的是确定是否可以将类似的复合生物标志物应用于该人群。研究设计：当开始IFALD（即直接胆红素2.0 mg/dL）治疗时，在基线时应用成人DILI标准。结果：共确定了214例在波士顿儿童医院接受治疗的IFALD患者; 168例患者符合分析条件。分析的大多数患者为男性（61%）和早产儿（87%）。碱性磷酸酶（ALP）2x正常值上限（ULN）捕获的DILI量最少（11%），而谷氨酰转移酶（GGT）1x ULN占最多（62%）。使用成人DILI标准，发现60例（39%）IFALD患者患有DILI。用GGT 1x ULN替代ALP 2x ULN可提高灵敏度，105例（69%）患者至少符合1项DILI标准。结论：许多挑战使得DILI标准难以应用于IFALD儿童。直接胆红素、部分ALP和GGT可能更合适。鉴于其复杂的病因和由于肝脏不成熟和生长而导致的年龄差异，需要开发更合适的复合标志物来评估该人群中的IFALD。
Background: Intestinal failure-associated liver disease (IFALD) is complex and diagnosed by concurrent use of parenteral nutrition, clinical presentation, and alterations in hepatic biomarkers exclusive of other causes of liver disease. In comparison with individual measures, composite biomarkers may provide a more effective means for assessing disease progression and response to treatment than single parameters. Since IFALD is considered by some to be a type of drug-induced liver injury (DILI), those diagnostic criteria could potentially be used in this population. Using a preexisting database of children treated for IFALD, our aim was to determine if a similar composite biomarker could be applied to this population. Study Design: Adult DILI criteria were applied at baseline, when treatment for IFALD (ie, direct bilirubin 2.0 mg/dL) was initiated. Results: A total of 214 patients with IFALD treated at Boston Children's Hospital were identified; 168 patients were eligible for analysis. Most patients analyzed were male (61%) and preterm (87%). Alkaline phosphatase (ALP) 2x upper limit of normal (ULN) captured the least amount of DILI (11%), while -glutamyltransferase (GGT) 1x ULN accounted for the most (62%). Using adult DILI criteria, 60 (39%) patients with IFALD were found to have DILI. Substituting GGT 1x ULN for ALP 2x ULN improved the sensitivity, with 105 (69%) of patients meeting at least 1 criterion for DILI. Conclusion: Numerous challenges made it difficult to apply the DILI criteria to children with IFALD. Direct bilirubin, fractionated ALP, and perhaps GGT may be more suitable. Given its complex etiology and the age-based differences due to hepatic immaturity and growth, a more suitable composite marker needs to be developed to assess IFALD in this population.