MRI Based Biomarkers in Pediatric Autoimmune Liver Disease

NCT03175471 | Recruiting

• 1 other identifier: CIN001-MRI biomarkers in AILD
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 1

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.

Conditions

Autoimmune Liver Disease; Primary Sclerosing Cholangitis; Autoimmune Hepatitis

Outcome Measures

Primary Outcomes (8)

• 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

• 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

• 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

• 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

• 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

• 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

• Serum based outcome

  Quantification of serum alkaline phosphatase (ALP in U/L) and Gamma-glutamyl transpeptidase (GGT in U/L).

  36 months

• 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 Outcomes (5)

• MR T1rho, T1, T2 Imaging

  36 Months

• Liver Morphometry

  36 Months

• Liver histopathology based outcomes

  36 Months

• Serum based outcomes

  36 Months

• Serum MMP7

  36 Months

Study Arms (1)

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.

Eligibility Criteria

• Age: 6 Years - 23 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 36799997 BACKGROUND

• 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.

  PMID: 35080454 RESULT

• 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.

  PMID: 38630086 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and serum samples, Liver biopsy tissue samples

MeSH Terms

Conditions

Cholangitis, Sclerosing; Hepatitis, Autoimmune

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Hepatitis, Chronic; Hepatitis; Liver Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Alexander Miethke, MD

  Cincinnati Childrens Hospital Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Miethke, MD

CONTACT

513-636-8948; Alexander.Miethke@cchmc.org

Cyd Castro Rojas, PhD

CONTACT

513-517-0580; Cyd.CastroRojas@cchmc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: June 5, 2017
• Study Start: January 17, 2017
• Primary Completion: January 30, 2026
• Study Completion (Estimated): January 30, 2027
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)