Clinical trial NCT03175471: MRI Based Biomarkers in Pediatric Autoimmune Liver Disease
Official title: Cross-sectional Study for Assessment of MRI Based Biomarkers of Bile Duct Injury and Hepatic Fibrosis in Pediatric Onset Autoimmune Liver Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autoimmune Liver Disease
Primary Sclerosing Cholangitis
Autoimmune Hepatitis
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2017-06-05
Enrollment: 115
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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).

Primary outcomes:
measure: MRI based outcomes
timeFrame: 36 months
measure: Liver histopathology based assessment of bile duct injury by ISHAK Score
timeFrame: 36 months
measure: Liver histopathology based assessment of bile duct injury by Ludwig score
timeFrame: 36 months
measure: Liver histopathology based assessment of liver fibrosis by Nakanuma score
timeFrame: 36 months
measure: Liver histopathology based assessment of liver fibrosis by Ishak score
timeFrame: 36 months
measure: Liver histopathology based assessment of cholangitis and hepatic activity
timeFrame: 36 months
measure: Serum based outcome
timeFrame: 36 months
measure: Enhanced Liver Fibrosis (ELF) score
timeFrame: 36 months
Secondary outcomes:
measure: MR T1rho, T1, T2 Imaging
timeFrame: 36 Months
measure: Liver Morphometry
timeFrame: 36 Months
measure: Liver histopathology based outcomes
timeFrame: 36 Months
measure: Serum based outcomes
timeFrame: 36 Months
measure: Serum MMP7
timeFrame: 36 Months
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
Study officials:
affiliation: Cincinnati Childrens Hospital Medical Center
name: Alexander Miethke, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Jun;48(6):1933-1944. doi: 10.1007/s00261-022-03733-9. Epub 2023 Feb 17.
citation: McCrary J, Trout AT, Mahalingam N, Singh R, Rojas CC, Miethke AG, Dillman JR. Associations Between Quantitative MRI Metrics and Clinical Risk Scores in Children and Young Adults With Autoimmune Liver Disease. AJR Am J Roentgenol. 2022 Jul;219(1):142-150. doi: 10.2214/AJR.21.27204. Epub 2022 Jan 26.
citation: Dillman JR, Trout AT, Taylor AE, Khendek L, Kasten JL, Sheridan RM, Sharma D, Karns RA, Castro-Rojas C, Zhang B, Miethke AG. Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease. AJR Am J Roentgenol. 2024 Jul;223(1):e2431108. doi: 10.2214/AJR.24.31108. Epub 2024 Apr 17.