MRI Based Biomarkers in Pediatric Autoimmune Liver Disease

Children's Hospital Medical Center, Cincinnati115 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

115

Conditions

Autoimmune Liver Disease Primary Sclerosing Cholangitis Autoimmune Hepatitis

Eligibility

Sex: ALLMin age: 6 YearsMax age: 23 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

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.

Time frame: 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).

Time frame: 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).

Time frame: 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) .

Time frame: 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).

Time frame: 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).

Time frame: 36 months

Serum based outcome

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

Time frame: 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).

Time frame: 36 months

Secondary Outcomes

MR T1rho, T1, T2 Imaging

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

Time frame: 36 Months

Liver Morphometry

Collagen deposition in percent area fibrosis by image analysis

Time frame: 36 Months

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).

Time frame: 36 Months

Serum based outcomes

Quantification of serum fractionated ALP (U/L)

Time frame: 36 Months

Serum MMP7

Quantification of serum MMP7 (pg/mL)

Time frame: 36 Months

MRI Based Biomarkers in Pediatric Autoimmune Liver Disease

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts