MRI Based Biomarkers in Pediatric Autoimmune Liver Disease

Primary Sclerosing Cholangitis Clinical Trial

Official title:

Cross-sectional Study for Assessment of MRI Based Biomarkers of Bile Duct Injury and Hepatic Fibrosis in Pediatric Onset Autoimmune Liver Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03175471
• Other study ID #: CIN001-MRI biomarkers in AILD
• Status: Recruiting
• Start date: January 17, 2017
• Est. completion date: January 30, 2027

Study information

• Verified date: March 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Alexander Miethke, MD
• Phone: 513-636-8948
• Email: Alexander.Miethke[@]cchmc.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 115
• Est. completion date: January 30, 2027
• Est. primary completion date: January 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 23 Years

Eligibility

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).

Related Conditions & MeSH terms

• Autoimmune Hepatitis
• Autoimmune Liver Disease
• Cholangitis
• Cholangitis, Sclerosing
• Hepatitis, Autoimmune
• Liver Diseases
• Primary Sclerosing Cholangitis

Locations

Country	Name	City	State
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

References & Publications (1)

Mahalingam N, Trout AT, Zhang B, Castro-Rojas C, Miethke AG, Dillman JR. Longitudinal changes in quantitative magnetic resonance imaging metrics in children and young adults with autoimmune liver disease. Abdom Radiol (NY). 2023 Feb 17. doi: 10.1007/s00261-022-03733-9. Online ahead of print. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRI based outcomes	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.	36 months
Primary	Liver histopathology based assessment of bile duct injury by ISHAK Score	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).	36 months
Primary	Liver histopathology based assessment of bile duct injury by Ludwig score	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).	36 months
Primary	Liver histopathology based assessment of liver fibrosis by Nakanuma score	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) .	36 months
Primary	Liver histopathology based assessment of liver fibrosis by Ishak score	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).	36 months
Primary	Liver histopathology based assessment of cholangitis and hepatic activity	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).	36 months
Primary	Serum based outcome	Quantification of serum alkaline phosphatase (ALP in U/L) and Gamma-glutamyl transpeptidase (GGT in U/L).	36 months
Primary	Enhanced Liver Fibrosis (ELF) score	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).	36 months
Secondary	MR T1rho, T1, T2 Imaging	Mean of MR T1rho, T1, T2 signal in msec to measure the inflammation.	36 Months
Secondary	Liver Morphometry	Collagen deposition in percent area fibrosis by image analysis	36 Months
Secondary	Liver histopathology based outcomes	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).	36 Months
Secondary	Serum based outcomes	Quantification of serum fractionated ALP (U/L)	36 Months
Secondary	Serum MMP7	Quantification of serum MMP7 (pg/mL)	36 Months