Chronic Liver Disease
Conditions
Keywords
liver fibrosis, liver cirrhosis, chronic hepatitis, magnetic resonance imaging
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.
Interventions
DRUGPerfusion 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.
Sponsors
Bachir Taouli
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PV Flow | 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. |
| PV Velocity | 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. |
| LS-MRE for Sub-Study I | 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. |
| True Diffusion Parameter (D) | 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 |
| LS-MRE Fibrosis State for Sub Study II | 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 |
| LS-TE | 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 |
| MTT | 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
| Measure | Time frame | Description |
|---|---|---|
| Liver DV | 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 |
| Liver Upslope From DCE-MRI | 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 |
| Spleen TTP | 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 |
| Liver Time to Peak (TTP) for PH | 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 |
| LS-MRE Portal Hypertension for Sub Study III | 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 |
| Spleen Volume | Fasting State Multiparametric MRI Scan (an average of 60 min) | Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg |
| Spleen Caudocranial Diameter | Fasting State Multiparametric MRI Scan (an average of 60 min) | Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg |
| PH Imaging Score | 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 |
| LSLU | 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 |
Countries
United States
Participant flow
Recruitment details
Recruitment began in May 2010, with enrollment from October 2010 through February 2017. Patients were recruited from the Division of Liver Diseases or from the Surgical Oncology Clinic at Mount Sinai.
Participants by arm
| Arm | Count |
|---|---|
| Perfusion MRI chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months.
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. | 214 |
| Healthy Volunteers Healthy Volunteers in Sub study I only | 11 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Sub Study I | Insufficient image quality | 0 | 10 |
| Sub Study II | Insufficient image quality | 3 | 0 |
| Sub Study II | No images in PACS | 1 | 0 |
| Sub Study II | Withdrawal by Subject | 1 | 0 |
| Sub Study III | Insufficient image quality | 5 | 0 |
| Sub Study V | Poor Image Quality | 2 | 0 |
| Total Participants | Insufficient image quality | 30 | 10 |
| Total Participants | No images in PACS | 10 | 0 |
| Total Participants | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Perfusion MRI | Healthy Volunteers | Total |
|---|---|---|---|
| Age, Continuous | 53.8 years | 30.6 years | 51.8 years |
| Age, Customized Sub Study I Chronic Hepatitis C patients | 55.8 years | 30.6 years | 46.5 years |
| Age, Customized Sub Study II | 55 years | — | 55 years |
| Age, Customized Sub Study III | 53 years | — | 53 years |
| Age, Customized Sub Study IV | 53 years | 29 years | 48 years |
| Age, Customized Sub Study V | 57 years | — | 57 years |
| Race/Ethnicity, Customized Asian | 31 Participants | 1 Participants | 32 Participants |
| Race/Ethnicity, Customized Black or African American | 20 Participants | 5 Participants | 25 Participants |
| Race/Ethnicity, Customized Hispanic | 38 Participants | 2 Participants | 40 Participants |
| Race/Ethnicity, Customized Unknown | 20 Participants | 0 Participants | 20 Participants |
| Race/Ethnicity, Customized White | 105 Participants | 3 Participants | 108 Participants |
| Sex: Female, Male Chronic Hepatitis C patients Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Chronic Hepatitis C patients Male | 17 Participants | 6 Participants | 23 Participants |
| Sex: Female, Male Female | 83 Participants | 5 Participants | 88 Participants |
| Sex: Female, Male Male | 32 Participants | 6 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 11 | 0 / 60 | 0 / 34 | 0 / 124 |
| other Total, other adverse events | 0 / 19 | 0 / 11 | 2 / 60 | 0 / 34 | 2 / 124 |
| serious Total, serious adverse events | 0 / 19 | 0 / 11 | 0 / 60 | 0 / 34 | 0 / 124 |
Outcome results
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Only 38 participants had suitable MRE quality for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | LS-MRE Fibrosis State for Sub Study II | F0-F2 | 2.88 kPa | Standard Deviation 0.91 |
| Chronic Hep C Patients | LS-MRE Fibrosis State for Sub Study II | F3-F4 | 5.16 kPa | Standard Deviation 0.95 |
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.
Time frame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
Population: Sub Study I with 30 participants. The method failed in 3 of the patients, so no usable LS-MRE data was generated. 27 patients had usable data for PV flow and velocity, so they were included in the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | LS-MRE for Sub-Study I | Fasting | 4.9 kPa | Standard Deviation 1.4 |
| Chronic Hep C Patients | LS-MRE for Sub-Study I | Postprandial | 5.0 kPa | Standard Deviation 1.2 |
| Healthy Volunteers | LS-MRE for Sub-Study I | Fasting | 1.8 kPa | Standard Deviation 0.2 |
| Healthy Volunteers | LS-MRE for Sub-Study I | Postprandial | 2.0 kPa | Standard Deviation 0.2 |
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
Time frame: Fasting transient elastography, average duration 10 min
Population: Only 46 participants had suitable TE quality for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | LS-TE | F0-F2 | 9.55 kPa | Standard Deviation 6.85 |
| Chronic Hep C Patients | LS-TE | F3-F4 | 21.44 kPa | Standard Deviation 17.86 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Only 50 participants had suitable quality MRI for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | MTT | F0-F2 | 11.6 seconds | Standard Deviation 8.1 |
| Chronic Hep C Patients | MTT | F3-F4 | 18.8 seconds | Standard Deviation 9.1 |
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.
Time frame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | PV Flow | Fasting | 16.0 ml/s | Standard Deviation 6.1 |
| Chronic Hep C Patients | PV Flow | Postprandial | 23.2 ml/s | Standard Deviation 8.5 |
| Healthy Volunteers | PV Flow | Fasting | 15.5 ml/s | Standard Deviation 4.2 |
| Healthy Volunteers | PV Flow | Postprandial | 27.1 ml/s | Standard Deviation 10.2 |
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.
Time frame: Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | PV Velocity | Fasting | 10.5 cm/s | Standard Deviation 3.2 |
| Chronic Hep C Patients | PV Velocity | Postprandial | 12.8 cm/s | Standard Deviation 4.6 |
| Healthy Volunteers | PV Velocity | Fasting | 11.5 cm/s | Standard Deviation 2.8 |
| Healthy Volunteers | PV Velocity | Postprandial | 14.4 cm/s | Standard Deviation 3.2 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min) Scan
Population: 3 participants with scans not evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | True Diffusion Parameter (D) | F0-F2 | 1.06 10^-3 mm^2/s | Standard Deviation 0.21 |
| Chronic Hep C Patients | True Diffusion Parameter (D) | F3-F4 | 0.94 10^-3 mm^2/s | Standard Deviation 0.16 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Among the 34 patients, 2 patients did not have DCE-MRI acquisition due to chronic renal insufficiency, 4 patients had non-usable DCE-MRI data because of major artifacts.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | Liver DV | HVPG<10mmHg | 47.28 percentage of liver volume | Standard Deviation 24.29 |
| Chronic Hep C Patients | Liver DV | HVPG>=10mmHg | 77.25 percentage of liver volume | Standard Deviation 111.01 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Among the 34 patients, 2 patients did not have DCE-MRI acquisition due to chronic renal insufficiency, 4 patients had non-usable DCE-MRI data because of major artifacts..
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | Liver Time to Peak (TTP) for PH | HVPG<5mmHg | 40.99 seconds | Standard Deviation 22.2 |
| Chronic Hep C Patients | Liver Time to Peak (TTP) for PH | HVPG>=5mmHg | 53.02 seconds | Standard Deviation 31.8 |
| Chronic Hep C Patients | Liver Time to Peak (TTP) for PH | HVPG<10mmHg | 41.47 seconds | Standard Deviation 25.76 |
| Chronic Hep C Patients | Liver Time to Peak (TTP) for PH | HVPG>=10mmHg | 69.45 seconds | Standard Deviation 41.98 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Among the 34 patients, 2 patients did not have DCE-MRI acquisition due to chronic renal insufficiency, 4 patients had non-usable DCE-MRI data because of major artifacts.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | Liver Upslope From DCE-MRI | HVPG <5mmHg | 0.011 mmol/(L.s)) | Standard Deviation 0.011 |
| Chronic Hep C Patients | Liver Upslope From DCE-MRI | HVPG>=5mmHg | 0.0007 mmol/(L.s)) | Standard Deviation 0.0007 |
| Chronic Hep C Patients | Liver Upslope From DCE-MRI | HPVG<10mmHg | 0.011 mmol/(L.s)) | Standard Deviation 0.007 |
| Chronic Hep C Patients | Liver Upslope From DCE-MRI | HPVG>=10mmHg | 0.0006 mmol/(L.s)) | Standard Deviation 0.004 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: 31 of the 34 participants had LS-MRE and 28 of the 34 participants had Liver Upslope measurement from DCE-MRI
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | LSLU | HVPG<5mmHg | 192.72 kPa*s*L/mmol | Standard Deviation 195.65 |
| Chronic Hep C Patients | LSLU | HVPG>=5mmHg | 830.28 kPa*s*L/mmol | Standard Deviation 971.68 |
| Chronic Hep C Patients | LSLU | HVPG<10mmHg | 363.68 kPa*s*L/mmol | Standard Deviation 855.01 |
| Chronic Hep C Patients | LSLU | HVPG>10mmHg | 871.82 kPa*s*L/mmol | Standard Deviation 1354.31 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: MRE was successful for liver stiffness measurements in 31 participants of the 34
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | LS-MRE Portal Hypertension for Sub Study III | HVPG<5mmHg | 2.31 kPa | Standard Deviation 2.8 |
| Chronic Hep C Patients | LS-MRE Portal Hypertension for Sub Study III | HVPG>=5mmHg | 5.14 kPa | Standard Deviation 2.57 |
| Chronic Hep C Patients | LS-MRE Portal Hypertension for Sub Study III | HVPG<10mmHg | 3.88 kPa | Standard Deviation 3.16 |
| Chronic Hep C Patients | LS-MRE Portal Hypertension for Sub Study III | HVPG>=10mmHg | 5.86 kPa | Standard Deviation 6.71 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Sub Study III with 34 participants
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | PH Imaging Score | HVPG<5mmHg | 0 score on a scale | Standard Deviation 1 |
| Chronic Hep C Patients | PH Imaging Score | HVPG>=5mmHg | 2 score on a scale | Standard Deviation 5.25 |
| Chronic Hep C Patients | PH Imaging Score | HVPG<10 | 1 score on a scale | Standard Deviation 1.5 |
| Chronic Hep C Patients | PH Imaging Score | HVPG>=10 | 4 score on a scale | Standard Deviation 4.5 |
Secondary
Spleen Caudocranial Diameter
Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Sub Study III with 34 participants
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | Spleen Caudocranial Diameter | HVPG<5mmHg | 11.6 cm | Standard Deviation 2.8 |
| Chronic Hep C Patients | Spleen Caudocranial Diameter | HVPG>=5mmHg | 14.0 cm | Standard Deviation 4.8 |
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
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Among the 34 patients, 2 patients did not have DCE-MRI acquisition due to chronic renal insufficiency, 4 patients had non-usable DCE-MRI data because of major artifacts.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | Spleen TTP | HVPG<10mmHg | 15.46 seconds | Standard Deviation 16.65 |
| Chronic Hep C Patients | Spleen TTP | HVPG>=10mmHg | 44.90 seconds | Standard Deviation 40.69 |
Secondary
Spleen Volume
Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg
Time frame: Fasting State Multiparametric MRI Scan (an average of 60 min)
Population: Sub Study III with 34 participants
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chronic Hep C Patients | Spleen Volume | HVPG<5mmHg | 246 cm^3 | Standard Deviation 252 |
| Chronic Hep C Patients | Spleen Volume | HVPG>=5mmHg | 441 cm^3 | Standard Deviation 629 |