Detection of Liver Fibrosis With Magnetic Resonance Imaging (MRI)

Chronic Liver Disease Clinical Trial

Official title:

Prospective Detection of Liver Fibrosis With MRI Compared to Fibroscan and Blood Tests

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01600105
• Other study ID #: GCO 09-1187
• Status: Completed
• Phase: Phase 4
• Start date: October 2010
• Est. completion date: July 31, 2017

Study information

• Verified date: January 2020
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 276
• Est. completion date: July 31, 2017
• Est. primary completion date: July 31, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Liver Disease
• Fibrosis
• Liver Cirrhosis
• Liver Diseases

Intervention

Drug:
• Perfusion MRI
1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bachir Taouli

Country where clinical trial is conducted

United States, 

References & Publications (3)

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 — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PV Flow	Sub-Study I Portal Venous Flow - forward flow during systole and early diastole, and flow reversal after atrial contraction.The average PV area was extracted, and PV flow was computed as the multiplication of area and velocity.	Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
Primary	PV Velocity	Sub-Study I Portal Venous Flow Velocity - The mean velocity of the region of interest (ROI) was extracted for each one of the 25 phase images, and the time average was computed.	Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
Primary	LS-MRE for Sub-Study I	Sub-Study I Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images.	Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
Primary	True Diffusion Parameter (D)	Sub-Study II True Diffusion Parameter - D- describes water diffusion in tissue independently from the effects of capillary perfusion; it is obtained from bi-exponential fitting of MRI diffusion signal acquired over a range of high and low diffusion-weighting factors (b-values); Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis	Fasting State Multiparametric MRI Scan (an average of 60 min) Scan
Primary	LS-MRE Fibrosis State for Sub Study II	Sub-Study II Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images.; Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis	Fasting State Multiparametric MRI Scan (an average of 60 min)
Primary	LS-TE	Sub-Study II Liver Stiffness with transient elastography (TE) (LS-TE) - a non-invasive modality of liver fibrosis detection: a shear wave is sent into the liver through a small transducer attached to an ultrasound probe, and the velocity of the wave is measured as it passes through the liver; shear wave velocity is then converted to stiffness, measured in kilopascals (kPa); Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis	Fasting transient elastography, average duration 10 min
Primary	MTT	Sub-Study II Mean Transit Time (MTT) - Liver Mean Transit Time of Contrast Agent through the tissue of interest from Dynamic Contrast Enhanced MRI; Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	Liver Upslope From DCE-MRI	Sub-Study III Liver Upslope of MRI signal is defined as peak concentration to the time to reach peak concentration of gadolinium contrast agent in the liver tissue of interest, derived from dynamic contrast-enhanced MRI (DCE-MRI.; Portal hypertension (PH), defined by hepatic venous pressure gradient (HVPG) =5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) =10 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	Liver Time to Peak (TTP) for PH	Sub-Study III Liver Time to Peak (TTP) is defined as the time in seconds to reach peak concentration of gadolinium contrast agent in the liver tissue of interest, derived from dynamic contrast-enhanced MRI (DCE-MRI) Portal hypertension (PH), defined by hepatic venous pressure gradient (HVPG) =5 mmHg Clinically Significant Portal Hypertension is defined as an HVPG =10 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	LS-MRE Portal Hypertension for Sub Study III	Sub-Study III Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images.; Portal Hypertension is defined as an HVPG =5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) =10 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	Spleen Volume	Sub-Study III Portal Hypertension is defined as an HVPG =5 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	Spleen Caudocranial Diameter	Sub-Study III Portal Hypertension is defined as an HVPG =5 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	PH Imaging Score	Sub-Study III Portal Hypertension imaging composite score (based on the presence of varices, spleen size, presence of ascites). The imaging score is based on the number of variceal sites (0: absence of varices, 1: one variceal site, 2: two variceal sites, and 3: 3 or more variceal sites), volume of ascites (0: no ascites, 1: minimal perihepatic and perisplenic fluid, 2: intraperitoneal fluid without marked abdominal wall distension, and 3: fluid causing marked abdominal wall distension), and maximum craniocaudal diameter of the spleen (0: size less than 13 cm, 1: size between 13 and 15 cm, 2: size between 15 and 20 cm, and 3: size greater than 20 cm). Score from 0 to 9, with higher score indicating worse disease.; Portal Hypertension is defined as an HVPG =5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) =10 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	LSLU	Sub-Study III Liver Stiffness to Liver Upslope ratio (LSLU) Portal Hypertension is defined as an HVPG =5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) =10 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	Liver DV	Sub Study III Liver Distribution Volume (DV) is the distribution volume of contrast agent in the tissue of interest defined as a percentage ratio of gadolinium material volume to the volume of the liver tissue of interest, as derived from DCE-MRI; in the case of a contrast agent with extracellular distribution, DV measures the intravascular and extravascular-extracellular volume.; Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) =10 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)
Secondary	Spleen TTP	Sub Study III Spleen Time To Peak (TTP) - time to reach peak gadolinium concentration in spleen tissue of interest, derived from DCE-MRI.; Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) =10 mmHg	Fasting State Multiparametric MRI Scan (an average of 60 min)