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NCT Number: NCT03175471

MRI Based Biomarkers in Pediatric 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.

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Key information

Conditions

Autoimmune Liver Disease Autoimmune Diseases Autoimmune Hepatitis Bile Duct Diseases Biliary Tract Diseases Cholangitis Cholangitis, Sclerosing Digestive System Diseases Hepatitis Hepatitis, Autoimmune Hepatitis, Chronic Immune System Diseases Liver Diseases Primary Sclerosing Cholangitis

Age range

6 year–23 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location status: Recruiting

Location contact

Alexander Miethke, MD

CONTACT

[email protected]

513-636-5581

Alexander Miethke, MD

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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).

Treatment and study plan

Primary outcomes

  1. 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.

  2. 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).

  3. 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).

  4. 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) .

  5. 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).

  6. 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).

  7. Serum based outcome

    Time frame: 36 months

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

  8. 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).

Secondary outcomes

  1. MR T1rho, T1, T2 Imaging

    Time frame: 36 Months

    Mean of MR T1rho, T1, T2 signal in msec to measure the inflammation.

  2. Liver Morphometry

    Time frame: 36 Months

    Collagen deposition in percent area fibrosis by image analysis

  3. 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).

  4. Serum based outcomes

    Time frame: 36 Months

    Quantification of serum fractionated ALP (U/L)

  5. Serum MMP7

    Time frame: 36 Months

    Quantification of serum MMP7 (pg/mL)

Study contacts

Contact information is provided by the study sponsor or research team.

Alexander Miethke, MD

CONTACT

[email protected]

513-636-8948

Cyd Castro Rojas, PhD

CONTACT

[email protected]

513-517-0580

Sponsors and collaborators

Lead sponsor

Children's Hospital Medical Center, Cincinnati

Other

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2026
Study completion
2027
First posted
Jun 5, 2017
Registry last updated
Dec 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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