MRI Based Biomarkers in Pediatric Autoimmune Liver Disease

March 1, 2023 updated by: Children's Hospital Medical Center, Cincinnati

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

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.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Anticipated)

115

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Childrens Hospital Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 23 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

A total of 115 patients between 6 and 23 years of age with a diagnosis of PSC or AIH will be enrolled.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Patients with autoimmune liver disease

Patients (6-23 y.o.) with established clinical diagnosis of AIH or suspected diagnosis of AIH based on elevated serum AST or ALT, elevated IgG level >1.1 ULN, elevated titer of autoantibodies, including ANA, SMA, LKM, LC-1 or SLA, which is consistent with the simplified criteria for the diagnosis of AIH in children will be enrolled.

Patients (6-23 y.o.) with established clinical diagnosis of PSC or Suspected diagnosis of PSC supported by abnormal cholangiogram (ERCP or MRCP) or elevated GGT>1.5 ULN and dilated bile ducts by liver ultrasound will be enrolled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MRI based outcomes
Time Frame: 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.
36 months
Liver histopathology based assessment of bile duct injury by ISHAK Score
Time Frame: 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).
36 months
Liver histopathology based assessment of bile duct injury by Ludwig score
Time Frame: 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).
36 months
Liver histopathology based assessment of liver fibrosis by Nakanuma score
Time Frame: 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) .
36 months
Liver histopathology based assessment of liver fibrosis by Ishak score
Time Frame: 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).
36 months
Liver histopathology based assessment of cholangitis and hepatic activity
Time Frame: 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).
36 months
Serum based outcome
Time Frame: 36 months
Quantification of serum alkaline phosphatase (ALP in U/L) and Gamma-glutamyl transpeptidase (GGT in U/L).
36 months
Enhanced Liver Fibrosis (ELF) score
Time Frame: 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).
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MR T1rho, T1, T2 Imaging
Time Frame: 36 Months
Mean of MR T1rho, T1, T2 signal in msec to measure the inflammation.
36 Months
Liver Morphometry
Time Frame: 36 Months
Collagen deposition in percent area fibrosis by image analysis
36 Months
Liver histopathology based outcomes
Time Frame: 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).
36 Months
Serum based outcomes
Time Frame: 36 Months
Quantification of serum fractionated ALP (U/L)
36 Months
Serum MMP7
Time Frame: 36 Months
Quantification of serum MMP7 (pg/mL)
36 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 17, 2017

Primary Completion (Anticipated)

January 30, 2026

Study Completion (Anticipated)

January 30, 2027

Study Registration Dates

First Submitted

January 31, 2017

First Submitted That Met QC Criteria

June 1, 2017

First Posted (Actual)

June 5, 2017

Study Record Updates

Last Update Posted (Actual)

March 2, 2023

Last Update Submitted That Met QC Criteria

March 1, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIN001-MRI biomarkers in AILD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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