MRI Based Biomarkers in Pediatric Autoimmune Liver Disease

Recruiting

• Conditions: Primary Sclerosing Cholangitis; Autoimmune Hepatitis; Autoimmune Liver Disease

• Registration Number: NCT03175471
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

Autoimmune liver diseases (AILD), which include Primary Sclerosing Cholangitis (PSC) and Autoimmune Hepatitis (AIH) are a common etiological factors for chronic liver disease among adolescents. In all these conditions, autoimmune lymphocyte responses are thought to orchestrate inflammatory injury against hepatocytes (primarily in AIH) or cholangiocytes (in PSC). In this proposal we aim to evaluate the Magnetic Resonance Imaging (MRI) modalities; MR cholangiopancreatography (MRCP) and MR elastography (MREL), as non-invasive biomarkers to assess two primary pathophysiological processes of AILD: bile duct damage and liver fibrosis. In this cross-sectional study MRI based findings of bile duct injury and liver fibrosis will be correlated with both liver histology and circulating biomarkers of these disease processes.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-17
• Study First Submitted: 2017-01-31
• Study First Submitted QC: 2017-06-01
• Study First Posted: 2017-06-05
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-12
• Primary Completion: 2026-01-30
• Study Completion: 2027-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 115

Inclusion Criteria

1. Age 6-23 years old.
2. Established or suspected clinical diagnosis of AIH or PSC.

Exclusion Criteria

1. History of liver transplantation.
2. Chronic Hepatitis B or untreated hepatitis C virus infection.
3. Pregnancy.
4. Absolute contraindication for MRI (e.g. pacemaker, metallic implants, claustrophobia).
5. Diagnosis of cystic fibrosis or biliary atresia
6. Diagnosis of cardiac hepatopathy.
7. Diagnosis of Wilson's disease, Alpha-1 Antitrypsin deficiency, or Glycogen storage disease.
8. Skin conditions which could be aggravated by MREL (i.e. Epidermolysis bullosa).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
MRI based outcomes	36 months	MRCP based assessment of intrahepatic and extrahepatic duct irregularities by Majoie classification (on 4 and 5 point scale of 0-3 and 0-4 respectively; 0: No visible abnormalities, 1: minimal dilatation/irregularities, 2: saccular dilatations/segmental stricture, 3: severe pruning, 4: Extremely irregular margin).; MREL based quantification of mean shear stiffness (kPa) of liver.
Liver histopathology based assessment of bile duct injury by ISHAK Score	36 months	Assessment of bile duct injury by ISHAK Score (Confluent necrosis: on the 7 point scale of 0-6; Focal necrosis on the 4 point scale of 0-4 and portal inflammation on the 4 point scale of 0-4).
Liver histopathology based assessment of liver fibrosis by Nakanuma score	36 months	Assessment of liver fibrosis by Nakanuma score for on the 4 point scale of 0-3 (0; No portal fibrosis, 1; Portal fibrosis; 2; Bridging fibrosis, 3; Liver cirrhosis) .
Liver histopathology based assessment of bile duct injury by Ludwig score	36 months	Assessment of bile duct injury by Ludwig score (on five point scale of 0-4; 0: No ductal injury, 1: portal inflammation, 2: periportal inflammation, 3: Portal bridging, 4: Nodular cirrhosis).
Liver histopathology based assessment of liver fibrosis by Ishak score	36 months	Assessment of liver fibrosis by Ishak score on the 7 point scale of 0-6 (0; Absent, 1; confluent necrosis, 2; necrosis in some areas, 3; necrosis in most areas, 4; necrosis with occasional portal-central bridging necrosis, 5; necrosis with multiple portal-central bridging necrosis, 6; Panacinar or multiacinar necrosis).
Liver histopathology based assessment of cholangitis and hepatic activity	36 months	Cholangitis and hepatic activity by Nakanuma score for on the 4 point scale of 0-3 (0; No bile duct loss, 1; Bile duct loss in \<1/3 of portal tracts; 2; Bile duct loss in 1/3-2/3 of portal tracts, 3; Bile duct loss in \>2/3 of portal tracts).
Serum based outcome	36 months	Quantification of serum alkaline phosphatase (ALP in U/L) and Gamma-glutamyl transpeptidase (GGT in U/L).
Enhanced Liver Fibrosis (ELF) score	36 months	Assesment of Enhanced Liver Fibrosis (ELF) score on continuous scale of 1-10; \<7.7 none -mild. ≥7.7 -\<9.8 moderate, \>9.8 sever).

Secondary Outcome Measures

Name	Time	Method
MR T1rho, T1, T2 Imaging	36 Months	Mean of MR T1rho, T1, T2 signal in msec to measure the inflammation.
Liver histopathology based outcomes	36 Months	Liver histopathology based grade of inflammation by Scheuer score on 5 point scale of 0-4; (0: No ductal injury, 1: portal inflammation, 2: periportal inflammation, 3: Portal to portal bridging, 4: Nodular cirrhosis).
Liver Morphometry	36 Months	Collagen deposition in percent area fibrosis by image analysis
Serum MMP7	36 Months	Quantification of serum MMP7 (pg/mL)
Serum based outcomes	36 Months	Quantification of serum fractionated ALP (U/L)

Trial Locations

Locations (1)

Cincinnati Childrens Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States