Clinical trial NCT01600105: Detection of Liver Fibrosis With Magnetic Resonance Imaging (MRI)
Official title: Prospective Detection of Liver Fibrosis With MRI Compared to Fibroscan and Blood Tests
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Liver Disease
Keywords: liver fibrosis
liver cirrhosis
chronic hepatitis
magnetic resonance imaging
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2012-05-16
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Patients with chronic liver disease are at high risk of developing liver scarring (fibrosis), with ultimate risks of cirrhosis and liver cancer that may require liver transplant. The investigators would like to develop non invasive advanced Magnetic Resonance Imaging (MRI) techniques (MR diffusion, perfusion and elastography) to assess the degree of liver damage in patients with chronic liver disease. These techniques combined could reach high diagnostic performance for detection of liver fibrosis; and could decrease the number of liver biopsies, which have risks and sample only a small portion of the liver.

Detailed description: Patients with chronic hepatitis have increased risks of liver damage, including fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma and end-stage liver disease requiring liver transplantation. These diseases are/will be the source of enormous health care costs and morbidity/mortality in the US.

Most hepatologists still rely on liver biopsy findings in patients newly diagnosed with chronic hepatitis, which enables the assessment of liver damage (fibrosis and inflammation). Liver biopsy has limitations, including cost, invasiveness, poor patient acceptance, limited sampling, inter-observer variability and is difficult to repeat.

Non invasive tests to capture the extent of liver damage at a larger scale are urgently needed. These will gain more acceptance among patients and hepatologists.

In this proposal, the investigators would like to test and validate non invasive MRI methods based on advanced MR diffusion, perfusion and elastography techniques for the detection of fibrosis and cirrhosis in patients with chronic hepatitis. In order to improve the diagnostic performance of MRI, the investigators would like to build and validate a predictive model based on advanced functional MRI metrics (diffusion, perfusion and elastography). If validated, this novel non invasive algorithm will not only decreases the number of liver biopsies, but also enable earlier diagnosis of liver fibrosis when antiviral treatment is more effective, and enable a comprehensive evaluation of the liver (to assess for cirrhosis, portal hypertension and hepatocellular cancer).

This could significantly reduce the cost of care, could become a useful tool for testing new antifibrogenic and antiviral drugs in chronic viral hepatitis, and could be used to follow patients for detection of progression to cirrhosis.

Eligibility criteria: Inclusion Criteria:

* Chronic liver disease (including viral hepatitis, alcoholic hepatitis, non alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, etc..)
* 18 years of age and older
* Liver biopsy (percutaneous or transjugular or surgical) performed within 6 months, as part of routine clinical care.
* Liver transplant or liver resection performed within 6 months, as part of routine clinical care.
* Patient is able to give informed consent for this study and agrees to provide a blood sample

Control group

* Patients without history of liver disease and healthy volunteers
* 18 years of age and older
* Subject is able to give informed consent for this study and agrees to provide a blood sample

Exclusion Criteria:

* Age less than 18 years
* Unable or unwilling to give informed consent
* Contra-indications to MRI
* Electrical implants such as cardiac pacemakers or perfusion pumps
* Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants
* Ferromagnetic objects such as jewelry or metal clips in clothing
* Pregnant subjects
* Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions.

Primary outcomes:
measure: PV Flow
timeFrame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
measure: PV Velocity
timeFrame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
measure: LS-MRE for Sub-Study I
timeFrame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
measure: True Diffusion Parameter (D)
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min) Scan
measure: LS-MRE Fibrosis State for Sub Study II
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: LS-TE
timeFrame: Fasting transient elastography, average duration 10 min
measure: MTT
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary outcomes:
measure: Liver Upslope From DCE-MRI
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: Liver Time to Peak (TTP) for PH
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: LS-MRE Portal Hypertension for Sub Study III
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: Spleen Volume
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: Spleen Caudocranial Diameter
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: PH Imaging Score
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: LSLU
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: Liver DV
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
measure: Spleen TTP
timeFrame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Bachir Taouli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jajamovich GH, Dyvorne H, Donnerhack C, Taouli B. Quantitative liver MRI combining phase contrast imaging, elastography, and DWI: assessment of reproducibility and postprandial effect at 3.0 T. PLoS One. 2014 May 19;9(5):e97355. doi: 10.1371/journal.pone.0097355. eCollection 2014.
citation: Dyvorne HA, Jajamovich GH, Bane O, Fiel MI, Chou H, Schiano TD, Dieterich D, Babb JS, Friedman SL, Taouli B. Prospective comparison of magnetic resonance imaging to transient elastography and serum markers for liver fibrosis detection. Liver Int. 2016 May;36(5):659-66. doi: 10.1111/liv.13058. Epub 2016 Feb 7.
citation: Wagner M, Hectors S, Bane O, Gordic S, Kennedy P, Besa C, Schiano TD, Thung S, Fischman A, Taouli B. Noninvasive prediction of portal pressure with MR elastography and DCE-MRI of the liver and spleen: Preliminary results. J Magn Reson Imaging. 2018 Oct;48(4):1091-1103. doi: 10.1002/jmri.26026. Epub 2018 Apr 11.
citation: Jajamovich GH, Calcagno C, Dyvorne HA, Rusinek H, Taouli B. DCE-MRI of the liver: reconstruction of the arterial input function using a low dose pre-bolus contrast injection. PLoS One. 2014 Dec 29;9(12):e115667. doi: 10.1371/journal.pone.0115667. eCollection 2014.