Methods to Detect Liver Fibrosis

Comparison of Non-invasive Methods to Detect and Quantify Liver Fibrosis

The goal of this study is to learn more about liver fibrosis and methods to detect it. We will evaluate and compare multiple MRI based measures of liver fibrosis in subjects with and without liver disease.

Study Overview

• Status: Terminated
• Conditions: Hepatic Steatosis; Liver Fibroses
• Intervention / Treatment: Device: MRI

Detailed Description

While liver biopsy is still considered the gold standard for diagnosing and assessing the presence and degree of liver fibrosis and inflammation, it has disadvantages including the potential for sampling error and risk of complications, including life-threatening bleeding. New imaging modalities such as MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer allow rapid, non-invasive evaluation of liver parenchymal characteristics and may be able to detect and quantify parenchymal fibrosis alleviating the need for biopsy. To date, the quantitative performance of these different techniques has not been extensively studied. This study is a single-center trial of non-invasive MR imaging techniques aimed at detecting and measuring liver fibrosis. Once optimized, these technologies may later be deployed in hypothesis driven research studies and/or routine clinical exams in the pediatric population here at CCHMC and/or as part of a multi-center study with specific IRB approval for that project.

To assess the relative performance of each technique, correlation across techniques, and reproducibility across the range of fibrosis, 32 subjects will be enrolled in this preliminary study sub-divided into 4 groups (Group 1: Healthy/ Normal controls; Group 2: F1/F2 fibrosis as determined by prior biopsy (low grade fibrosis group); Group 3: F3/F4 fibrosis as determined by prior biopsy (high grade fibrosis group), Group 4: Hepatic steatosis with fibrosis (NAFLD group)). 8 healthy subjects without known or suspected liver disease will be enrolled as normal controls. 8 subjects each with known fibrosis based on liver biopsy within the last 6 months will be enrolled in Group 2 and Group 3 (total = 16). 8 subjects with known hepatic steatosis and liver fibrosis based on liver biopsy within the last 6 months will be enrolled in Group 4.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Group 1:

1. Healthy subjects with no known or suspected liver disease
2. Age 8 - 21 years

Groups 2 and 3:

1. Biopsy confirmed liver fibrosis (F1/F2 Group 2, F3/F4 Group 3)
2. Age 8 - 21 years

Group 4:

1. Biopsy confirmed hepatic steatosis AND biopsy confirmed liver fibrosis (any stage)
2. Age 8 - 21 years

Exclusion Criteria

All subjects:

1. Subjects <8 years of age and >21 years of age.
2. BMI > 35 kg/m2
3. Subjects deemed to possibly require sedation to undergo MR imaging
4. Inability to lie still for 90 minutes
5. Routine exclusions to MRI - e.g., implanted hardware
6. Pregnancy (verbal pregnancy screens - per standard practice in Radiology - will be administered to all female participants of child-bearing age at the time of enrollment and again immediately prior to imaging)
7. Prior history of liver transplantation

Group 1

1. ALT ≥30 U/L
2. Clinical history or lab/biopsy results suggestive of the presence of liver disease including: steatosis, fibrosis, inflammation, tumor, etc.

Group 2 and 3

1. Diagnosis of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis
2. Biopsy >6 months prior to research MRI examination
3. Initiation of any medications (e.g. steroids, immunosuppressants, antivirals) or procedures (e.g. Kasai portoenterostomy) to treat the liver disease during the time between liver biopsy and study visit

Group 4

1. Biopsy >6 months prior to research MRI examination
2. Hepatic fat fraction >5%
3. Substantial weight loss (>10% of weight at time of biopsy) during the time between biopsy and study visit
4. Initiation of any medications to treat NAFLD (e.g. vitamin E) during the time between biopsy and study visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Health/Normal Controls; Health/normal control subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.	Device: MRI; MRI scan performed on 1.5T Philips Ingenia MRI scanner.
Active Comparator: F1/F2 fibrosis; Type 1 and 2 liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.	Device: MRI; MRI scan performed on 1.5T Philips Ingenia MRI scanner.
Active Comparator: F3/F4 fibrosis; Type 2 and 3 liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.	Device: MRI; MRI scan performed on 1.5T Philips Ingenia MRI scanner.
Active Comparator: Hepatic steatosis with fibrosis; Hepatic steatosis with liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.	Device: MRI; MRI scan performed on 1.5T Philips Ingenia MRI scanner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MR imaging vs. histologic scoring in hepatic fibrosis	Correlate the results from the different imaging sequences designed to detect and quantify hepatic fibrosis	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI reproducibility	evaluate the reproducibility of each of the tested MRI-based liver fibrosis quantification sequences	2 years

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• Sporea I, Bota S, Jurchis A, Sirli R, Gradinaru-Tascau O, Popescu A, Ratiu I, Szilaski M. Acoustic radiation force impulse and supersonic shear imaging versus transient elastography for liver fibrosis assessment. Ultrasound Med Biol. 2013 Nov;39(11):1933-41. doi: 10.1016/j.ultrasmedbio.2013.05.003. Epub 2013 Aug 9.
• Xanthakos SA, Podberesky DJ, Serai SD, Miles L, King EC, Balistreri WF, Kohli R. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr. 2014 Jan;164(1):186-8. doi: 10.1016/j.jpeds.2013.07.050. Epub 2013 Sep 21.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2017
• Primary Completion (Actual): December 30, 2018
• Study Completion (Actual): December 30, 2018

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: January 19, 2017
• First Posted (Estimate): January 23, 2017

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 27, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Fatty Liver; Liver Cirrhosis
• Other Study ID Numbers: CIN001- Liver Fibrosis

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