FibroScan in Pediatric Cholestatic Liver Disease

Non-invasive monitoring of liver fibrosis is an unmet and critical need within the clinical management of children with chronic liver disease. While liver biopsy is often used in the initial diagnostic evaluation of children with liver disease, subsequent surveillance liver biopsy is rarely performed in children because of its inherent invasiveness and risks. Therefore, our understanding of the natural history of fibrosis progression in children is limited. The patchy nature of fibrosis in many important pediatric liver diseases (e.g., biliary atresia (BA) and cystic fibrosis liver disease (CFLD)) limits the utility of sequential liver biopsy even if it were to be employed in clinical practice in pediatrics. Thus, non-invasive means of assessing liver fibrosis throughout the liver would be highly desirable and clinically useful in pediatric hepatology. The Childhood Liver Disease Research Network (ChiLDReN) is poised and uniquely qualified to conduct a comprehensive longitudinal assessment of the utility of FibroScan™-specific elastography, liver stiffness measurement (LSM) as a measure of hepatic fibrosis in children with serious chronic cholestatic liver disease. The FibroScan in Pediatric Cholestatic Liver Disease (FORCE) study, a natural history study within ChiLDReN, was a cross-sectional and longitudinal assessment of the utility of LSM in children with chronic cholestatic liver disease. Study participants were from 13 ChiLDReN sites in the U.S. and Canada, and were also enrolled in the PROBE, BASIC, or LOGIC studies. FORCE participants were evaluated for a period of up to 24 months to assess the non-invasive ultrasound tool (FibroScan™) to detect and quantify global liver fibrosis in children with biliary atresia (BA), alpha-1 antitrypsin deficiency (A1ATD), and Alagille syndrome (ALGS). The participants were non-fasted and non-sedated during data collection. There were three visits in the study: baseline, 12-month follow-up, and 24-month follow-up. Clinical data and biosamples were collected at each visit along with repeated FibroScan measurements such as liver stiffness measurements (LSM) to quantify liver fibrosis, and controlled attenuation parameter (CAP) to quantify liver steatosis. Baseline data are available from the Repository.慢性肝病患儿的临床管理中，无创监测肝纤维化（liver fibrosis）是一项尚未满足的关键临床需求。尽管肝活检（liver biopsy）常被用于肝病患儿的初始诊断评估，但由于其固有侵入性与风险，儿童群体中极少开展后续的监测性肝活检。因此，我们对儿童肝纤维化进展自然史的认知十分有限。许多重要的儿童肝病（如胆道闭锁（biliary atresia, BA）与囊性纤维化肝病（cystic fibrosis liver disease, CFLD））中，纤维化呈斑片状分布的特性即便在儿科临床实践中开展连续肝活检，也会限制其应用价值。因此，能够全面评估全肝肝纤维化的无创手段，在儿童肝病学（pediatric hepatology）领域极具应用价值与临床意义。 儿童肝病研究网络（Childhood Liver Disease Research Network, ChiLDReN）已准备就绪且具备独特资质，可针对严重慢性胆汁淤积性肝病患儿开展一项全面的纵向评估，以验证基于FibroScan™的弹性成像技术、肝脏硬度测定（liver stiffness measurement, LSM）作为肝纤维化评估指标的应用价值。 儿童胆汁淤积性肝病中的FibroScan研究（FibroScan in Pediatric Cholestatic Liver Disease, FORCE）是ChiLDReN旗下的一项自然史研究，旨在对LSM在慢性胆汁淤积性肝病患儿中的应用价值开展横断面与纵向评估。本研究的受试者来自美国与加拿大的13个ChiLDReN研究中心，且同时参与了PROBE、BASIC或LOGIC研究。FORCE研究的受试者被随访长达24个月，以评估这款无创超声工具（FibroScan™）在胆道闭锁（BA）、α1-抗胰蛋白酶缺乏症（alpha-1 antitrypsin deficiency, A1ATD）以及阿拉基综合征（Alagille syndrome, ALGS）患儿中检测并量化全肝肝纤维化的能力。数据采集期间，受试者无需禁食、无需镇静。本研究共设置三次访视：基线访视、12个月随访访视以及24个月随访访视。每次访视均会收集临床数据与生物样本，同时重复开展FibroScan检测，包括用于量化肝纤维化的肝脏硬度测定（LSM），以及用于量化肝脂肪变性的受控衰减参数（controlled attenuation parameter, CAP）。 基线数据可从数据库（Repository）获取。