Assessing Kids for Liver Inflammation and Fibrosis Using Non-invasive MRI

Completed

• Conditions: Non-alcoholic Steatohepatitis; Liver Diseases; Autoimmune Hepatitis; Liver Fibroses; Liver Cirrhoses
• Interventions: Device: MRI

• Registration Number: NCT03198104
• Lead Sponsor: Perspectum

Brief Summary

This is a prospective observational study which will recruit up to 100 paediatric participants over a period of 30 months to determine whether MRI is as accurate at detecting, distinguishing, and monitoring liver disease as current standard of care techniques such as liver biopsy and fibroscan.

Detailed Description

The most serious pandemic facing Europe is fatty liver disease and non-alcoholic steatohepatitis (NASH). The main causal factor is obesity: according to recent statistics 11.8m-16.3m European children are overweight, of which 2.9m - 4.4m are obese. Unfortunately, current techniques for the diagnosis and monitoring of liver disease in children are poor. Available methods are either insensitive, such as blood tests, or invasive, i.e. liver biopsy, which is risky, painful, and costly. Although it is currently considered to be the gold standard for tissue assessment, liver biopsy has severe limitations, one of which is that it samples only a tiny fraction of the liver, and so it cannot give a representative diagnosis when liver disease is regional. Early determination of liver diseases in children, could have a significant impact on changing the course of illness and on the proper treatment management.

Perspectum Diagnostics have demonstrated that multiparametric MR imaging can, for the first time, allow accurate, non-invasive detection of liver fibrosis/inflammation in adults, and predict clinical outcomes (1,2). However, liver disease in children differs from adults in aetiology, natural history and pathological findings (3,4).

This study will investigate whether non-invasive multiparametric MR imaging of the liver can accurately and reproducibly detect, distinguish and track progression of different forms of liver disease in the paediatric population. To achieve this, children with liver disease who are scheduled to undergo liver biopsy and blood tests as part of their standard care will be recruited. Non-invasive, pain-free MRI scanning will be used to measure fibrosis, iron content and fat content of liver tissue and compare these results to the findings of the liver biopsy that is being performed as standard care. Children who are scheduled to receive repeated liver biopsies to monitor their response to the treatment of autoimmune hepatitis as part of their usual care will also be included. Repeated MRI scans will be performed and compared with the results of biopsy findings.

Study Timeline

• Study Start: 2016-04-01
• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-21
• Study First Posted: 2017-06-23
• Primary Completion: 2019-03-01
• Study Completion: 2019-03-31
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-29
• Last Update Posted: 2019-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

Group 1 (Liver disease):

• Male or female between 6 - 18 years of age
• Male or female aged between 1-10 years of age and scheduled to receive an MRI under anesthesia as part of their standard care.
• Scheduled to receive an ultra-sound guided liver biopsy as part of their usual care
• Participant and guardian are willing and able to give assent and consent for participation in the study

Group 2 (AIH):

• Male or female between 6 - 18 years of age
• Male or female aged between 1-10 years of age and scheduled to receive an MRI under anesthesia as part of their standard care.
• Diagnosed with autoimmune hepatitis and due to begin liver-biopsy monitored treatment as part of their usual care
• Participant and guardian are willing and able to give assent and consent for participation in the study

Group 3 (Healthy controls):

• Male or female between 6 - 18 years of age (age-matched with Group 1)
• Lean, defined as within interquartile range for age and sex-matched childhood BMI growth charts
• Healthy, with no active medical condition requiring treatment, including diabetes, hypertension, psoriasis and any chronic gastrointestinal disorder
• Participant and guardian are willing and able to give assent and consent for participation in the study

Exclusion Criteria

• The participant may not enter the study if they have any contraindication to magnetic resonance imaging (inc pregnancy, extensive tattoos, pacemaker, shrapnel injury, severe claustrophobia).
• Any other cause, including a significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy Volunteers	MRI	Healthy volunteers (20-30 children) will be scanned using MRI and fibroscan and used as healthy controls.
Liver disease	MRI	Paediatric patients (50-60 pts.) with liver disease who are scheduled for an ultrasound-guided liver biopsy as part of their standard care - these patients will be scanned using MRI and fibroscan, then will proceed through standard care pathway to receive blood tests and a liver biopsy. Findings from the fibroscan, blood tests and liver biopsy will be compared to the MRI data to determine it's accuracy in detecting and distinguishing different types of liver disease.
Autoimmune Hepatitis Group (AIH)	MRI	Paediatric patients who have been diagnosed with autoimmune hepatitis and are about to initiate pharmacological treatment (15-30 pts.) will be scanned using MRI and fibroscan, then proceed through the standard care pathway to receive repeated blood tests and liver biopsies throughout treatment. MRI and fibroscan will be repeated before each liver biopsy. Findings from the fibroscan, blood tests and liver biopsy will be compared to MRI data to determine it's accuracy in monitoring liver disease.

Primary Outcome Measures

Name	Time	Method
Multiparametric non-invasive MRI of liver tissue in detecting and distinguishing different forms of paediatric liver disease.	30 months	Measurements using multiparametric MRI and comparison of these results with liver biopsy findings.

Secondary Outcome Measures

Name	Time	Method
Determining use of MRI in measuring changes in liver disease within patient.	30 months	Measurements using repeated MRI and comparison of these results with repeated paediatric liver biopsy findings throughout the course of treatment for autoimmune hepatitis.

Trial Locations

Locations (1)

Children's Memorial Health Institute Poland; 🇵🇱 Warsaw, Poland