Imaging-Based Biomarkers for Non-Invasive Pediatric Liver Diagnostics
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 550
- 试验地点
- 1
- 主要终点
- Diagnostic accuracy of ultrasound-based liver biomarkers (SWE, SWD, ATI) (STUDY 1)
研究概览
简要总结
The goal of this observational (diagnostic validation) study is to validate imaging-based biomarkers for assessing liver involvement in pediatric patients with established or suspected liver disease. The projekt involves 3 larger studies, each with specific aims specified in detailed description below.
The main study (study 1) compares imaging-based biomarkers-with liver biopsy to evaluate their correlation with histologically confirmed liver disease, including fibrosis, inflammation, and steatosis. The main question the overall project aims to answer is:
• Can multiple novel imaging-based biomarkers, such as shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI), be used for detailed, non-invasive liver characterization in children, and if so, how should they be used?
详细描述
The purpose is to improve diagnostics and surveillance in children with liver disease and reduce the need for biopsies. The overall aim is to test the hypothesis that multiple novel imaging-based biomarkers can be used to diagnose and phenotype liver disease non-invasively. Specifically, we will evaluate if the imaging-based biomarkers shear wave elastography (SWE), shear wave dispersion (SWD) and attenuation coefficient image (ATI) can differentiate between various pathoanatomic phenotypes (fibrosis/inflammation/ steatosis) associated with liver disease and to determine if these imaging-based biomarkers can be used for detailed, non-invasive liver characterization in children.
Specific aims
- To determine if SWE, SWD and ATI can be used as quantitative imaging-based biomarkers for fibrosis, inflammation and steatosis of the liver in children, and to establish cut-off values for grades of disease.
- To identify interactions between imaging-based biomarkers and serology, age, sex, free-breathing, weight, BMI, cholestasis, necrosis, and congestion in children.
- To evaluate the imaging-based biomarkers longitudinally to monitor treatment effects and determine if these biomarkers can improve surveillance of disease, compared to conventional ultrasound/clinical biomarkers, in children with liver transplants, cystic fibrosis, obesity and intestinal failure-associated liver disease (IFALD).
- To compare the relationship between regional tissue characterization with ultrasound and global characterization with magnetic resonance imaging (MRI)
The project includes 3 studies, each planned to generate several manuscripts, planned to answer the 4 specific aims. The studies will be conducted according to the Declaration of Helsinki. Ethical approval has been obtained (Dnr;634-18, 2021-06760-02, 2022-01046-02, 2022-01661-02).
Study 1: Validation of multiple ultrasound-based liver biomarkers (SWE/SWD/ATI) Study 2: Surveillance of disease and treatment - longitudinal monitoring with SWE/SWD/ATI Study 3: MR elastography (MRE)
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •technical limitations regarding the measurements
- •inability to fully understand the informed consent documents.
结局指标
主要结局
Diagnostic accuracy of ultrasound-based liver biomarkers (SWE, SWD, ATI) (STUDY 1)
时间窗: At time of liver biopsy
Primary outcome study 1 To evaluate the sensitivity, specificity, and correlation of SWE (for fibrosis), SWD (for inflammation), and ATI (for steatosis) against histologically confirmed liver disease in pediatric patients. Using Area under the ROC curve (AUC), sensitivity, specificity, correlation coefficients
Longitudinal change in SWE/SWD/ATI biomarkers before and after treatment with CFTR modulators, (Study 2A - Children with Cystic Fibrosis)
时间窗: baseline (pretreatment) up to 2 years
Evaluate the effect of CFTR modulator therapy on liver biomarkers. Metric: Change in SWE/SWD/ATI values over time
Change in liver biomarkers measured by SWE and SWD during routine ultrasound surveillance post-liver transplantation. (Study 2b)
时间窗: Up to 1 year
SWE and SWD will be added to conventional ultrasound to assess liver stiffness and viscocity. These imaging biomarkers will be tracked longitudinally to evaluate their utility in improving post-transplant surveillance.
Detection of early liver damage using SWE, SWD, and ATI (Attenuation Imaging) in children with intestinal failure. (Study 2c)
时间窗: up to 2 years
Non-invasive ultrasound biomarkers will be measured during yearly check-ups to identify early signs of liver fibrosis and steatosis in children at risk of IFALD
Change in SWE/SWD/ATI biomarkers following obesity treatment (GLP-1 analogues or bariatric surgery) (Study2d)
时间窗: through study completion, an average of 1 years
Assess whether imaging biomarkers reflect early liver response to obesity interventions. Metric: Change in SWE/SWD/ATI values over time
Correlation between ultrasound biomarkers and MR biomarkers . (Study 3)
时间窗: periprocedurally
SWE/SWD/ATI and MRE will be performed within a 2 week period and compared to assess the relationship between regional and global liver stiffness and steatosis measurements.
次要结局
- Association between imaging biomarkers and blood liver markers and demographic variabels (Study 1)(periprocedurally)
- Correlation between SWE/SWD values and clinical outcomes in livertransplats . (Study 2b)(From enrollment to 1 year)
- Correlation between SWE/SWD/ATI values and serological liver markers (Study 2c)(from enrollment to 2 years)
- Correlation between MRE and histological findings from liver biopsy. (study3)(periprocedurally)
研究者
Hannah Hebelka
Associate Professor
Sahlgrenska University Hospital