Serologic test for neonatal hemochromatosis in infants with acute liver failure

急性肝功能衰竭婴儿新生儿血色素沉着症的血清学检测

• 批准号: 7808933
• 负责人: PETER Frank WHITINGTON
• 金额: $ 28.07万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7808933
• 关键词: Acute Liver Failure; Address; Affect; Age; Antibodies; Area; Binding; Biological Assay; Biological Markers; Child; Childhood; Clinical; Clinical Research; Collaborations; Collection; Complement; Complement Membrane Attack Complex; Diagnosis; Diagnostic; Etiology; Fetal Liver; Funding; Goals; Gold; Hemochromatosis; Hepatic; Hepatocyte; Histopathology; Immunofluorescence Immunologic; Immunoglobulin G; Infant; Infant Mortality; Injury; Investigation; Knowledge; Lead; Life; Liver; Liver Failure; Liver diseases; Mediating; Medical; Methods; Morbidity - disease rate; Mothers; Neonatal; Outcome; Patients; Population; Population Study; Prevalence; Qualifying; Research; Sampling; Sensitivity and Specificity; Series; Serologic tests; Serum; Siderosis; Staging; Testing; Validation; Woman; Work; age group; conventional therapy; diagnostic accuracy; fetal; improved; innovation; isoimmunity; liver transplantation; maternal serum; mortality; neonatal morbidity; neonate; novel; novel diagnostics; public health relevance; repository; tool

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (04) Clinical Research and specific Challenge 04-DK-104 Improve the diagnosis, staging and treatment of diseases of the liver. This application specifically seeks to develop an approach that will improve the diagnosis of acute liver failure in infants, result in significantly improved outcome with medical therapy, and reduce the utilization of liver transplantation in pediatric patients. Neonatal hemochromatosis (NH) is the leading diagnosed cause of liver failure in neonates in most series. However, no diagnosis for acute liver failure can be established in up to 40% of infants. The overall objective of this application is to determine the true prevalence of NH as a cause of acute liver failure in infants d 90 days of age. The critical gap in scientific knowledge to be overcome before its importance as cause of acute liver failure can be determined is the lack of a sensitive and specific diagnostic biomarker for NH. Since NH is caused by maternal alloimmunity against fetal liver, the biomarker proposed is the presence of "anti-fetal hepatocyte IgG antibody" in mothers' or infants' serum. The diagnostic utility of an immunofluorescence assay for this biomarker is to be established and then it will be used to assess the prevalence of NH in a population of young infants with acute liver failure. Normally acquiring a study population large enough to power such a study would require many years of study. However, sera obtained from the Pediatric Acute Liver Failure study repository will be used, making it feasible to complete the proposed work within the timeframe of two years. The expected results will show that NH constitutes fully 50% of all causes of acute liver failure in young infants. This finding will have a significant positive impact because NH is responsive to specific medical therapy, which improves outcome over current treatment including liver transplantation. Furthermore, should the novel test used in this analysis prove to be sensitive and specific for the diagnosis, it could replace current diagnostic approaches and prospectively improve diagnostic accuracy in this setting. Thus, early, precise diagnosis could lead to improved outcome and reduced utilization of liver transplantation. PUBLIC HEALTH RELEVANCE: Neonatal Hemochromatosis (NH) is an important cause of liver failure in infants, but the diagnosis may be easily missed. A novel serological test will be used to determine if NH is the cause of the nearly 40% of pediatric acute liver failure without diagnosis. Since NH is responsive to medical treatment, improving the diagnosis of acute liver failure could save the lives of many infants and substantially reduce the need for liver transplantation in children.

描述（由申请人提供）：此申请解决广泛的挑战领域（04）临床研究和特定挑战04-DK-104改善肝脏疾病的诊断，分期和治疗。该应用专门旨在开发一种方法，该方法将改善婴儿急性肝衰竭的诊断，从而显着改善医疗疗法的预后，并减少儿科患者肝移植的利用。新生儿血色素沉着病（NH）是大多数系列新生儿肝衰竭的主要原因。但是，在多达40％的婴儿中，无法确定急性肝衰竭的诊断。该应用的总体目的是确定NH作为急性肝衰竭D 90天大的原因。在可能确定急性肝衰竭的原因之前，要克服的科学知识的关键差距是缺乏NH敏感且特定的诊断生物标志物。由于NH是由母体同种免疫性针对胎儿肝脏引起的，因此提出的生物标志物是母亲或婴儿血清中存在“抗狂热肝细胞IgG抗体”。要建立对该生物标志物的免疫荧光测定法的诊断效用，然后将其用于评估急性肝衰竭的年轻婴儿中NH的患病率。通常，获得足够大以为这样的研究供电的研究人群需要多年的研究。但是，将使用从小儿急性肝衰竭研究存储库中获得的血清，这使得在两年时间内完成建议的工作是可行的。预期的结果将表明，NH占年轻婴儿急性肝衰竭的所有原因的完全50％。这一发现将产生重大的积极影响，因为NH对特定的药物疗法有反应，这改善了包括肝移植在内的当前治疗结果。此外，如果在此分析中使用的新型测试被证明是敏感且特异性的，则可以取代当前的诊断方法，并在这种情况下前瞻性提高诊断准确性。因此，早期，精确的诊断可能会导致肝移植的结果改善和减少的利用率。 公共卫生相关性：新生儿血色素沉着症（NH）是婴儿肝衰竭的重要原因，但诊断可能很容易错过。新的血清学检查将用于确定NH是否是未经诊断的小儿急性肝衰竭的原因。由于NH对医疗有反应，因此改善急性肝衰竭的诊断可以挽救许多婴儿的生命，并大大减少儿童肝移植的需求。