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NCT Number: NCT01600105

Detection of Liver Fibrosis With Magnetic Resonance Imaging (MRI)

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.

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Key information

Conditions

Chronic Liver Disease Chronic Disease Digestive System Diseases Disease Attributes Fibrosis Hepatitis Hepatitis, Chronic Liver Cirrhosis Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Icahn School of Medicine at Mount Sinai

New York, 10029, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

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

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.

Treatment and study plan

Perfusion MRI

Drug
  • 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.

Other names: Dynamic contrast-enhanced MRI, Perfusion MRI (adofosveset trisodium, Ablavar, Lantheus)

Primary outcomes

  1. PV Flow

    Time frame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)

    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.

  2. PV Velocity

    Time frame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)

    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.

  3. LS-MRE for Sub-Study I

    Time frame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)

    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.

  4. True Diffusion Parameter (D)

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min) Scan

    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

  5. LS-MRE Fibrosis State for Sub Study II

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

  6. LS-TE

    Time frame: Fasting transient elastography, average duration 10 min

    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

  7. MTT

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

Secondary outcomes

  1. Liver Upslope From DCE-MRI

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

  2. Liver Time to Peak (TTP) for PH

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

  3. LS-MRE Portal Hypertension for Sub Study III

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

  4. Spleen Volume

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg

  5. Spleen Caudocranial Diameter

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg

  6. PH Imaging Score

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

  7. LSLU

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

  8. Liver DV

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

  9. Spleen TTP

    Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)

    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

Sponsors and collaborators

Lead sponsor

Bachir Taouli

Other

Registry information

Official study title

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

Important dates

Study start
2010
Primary completion
2017
Study completion
2017
First posted
May 16, 2012
Registry last updated
Feb 7, 2020

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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