Hepatitis CELFNCT02044523
Noninvasive Staging of Liver Fibrosis: MR vs Ultrasound
An observational study of Hepatitis C and Hepatitis B, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial summary
Liver fibrosis is an important public health problem, with a substantial morbidity and mortality due to progression to cirrhosis and hepatocellular carcinoma. All causes of chronic liver disease may lead to fibrosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Hepatitis B, Nonalcoholic Fatty Liver Disease (NAFLD)
- What is being tested?
- Transient elastography, acoustic radiation force impulse, magnetic resonance elastography
- Type of treatment
- Medical device
- How many people
- 108 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2014to Jun 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The target population is adults with any of the three main causes of liver fibrosis: HBV, HCV or NASH. For the purpose of this study, we will recruit patients seen at the hepatology clinic of St-Luc Hospital, a tertiary care center.
Who may be able to join
- are adults;
- must undergo a liver biopsy as part of their clinical standard of care for suspected or known chronic liver disease caused by HBV, HCV or NASH;
- understand French or English instruction;
- Autoimmune Hepatitis
Who cannot join
- have any contra-indication to MRI (such as claustrophobia, pacemaker, metallic clips for a neurosurgical procedure);
- are pregnant or trying to become pregnant;
- have a weight or girth preventing them from entering the MR magnet bore;
- are unable to understand or unwilling to provide written informed consent for this study.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, H2X 0A9
About this study
Official title: Comparison of Magnetic Resonance and Ultrasound Elastography With Liver Biopsy for Noninvasive Staging of Liver Fibrosis
Liver fibrosis is an important public health problem, with a substantial morbidity and mortality due to progression to cirrhosis and hepatocellular carcinoma. All causes of chronic liver disease may lead to fibrosis. The traditional diagnostic approach requires a biopsy for assessing the severity of liver disease prior to therapy.
However, liver biopsy has several limitations: cost, sampling error, and procedure-related morbidity and mortality. Considering the high prevalence of viral hepatitis and nonalcoholic fatty liver disease, a condition often associated with obesity and type 2 diabetes, there is an urgent need for noninvasive screening, diagnosis and monitoring strategies of chronic liver disease severity.
Read more
Our team has the expertise to investigate ultrasound-based and magnetic resonance-based elastographic methods for the noninvasive staging of liver fibrosis.
The primary objective of this cross-sectional study is to compare the sensitivity of elastographic methods for detecting histology-determined significant fibrosis.
The secondary objectives are to compare the diagnostic accuracy of these elastographic methods and the influence of potential confounders (inflammation, steatosis and iron deposition) on their diagnostic accuracy.
Read the detailed description
Background: Liver fibrosis is an important public health problem, with a substantial morbidity and mortality due to cirrhosis (the end stage) and hepatocellular carcinoma. All causes of chronic liver disease may lead to fibrosis. The amount of fibrosis determines the prognosis and influences the response to treatment of chronic liver disease.
Several elastographic methods have been proposed for noninvasive detection and staging of liver fibrosis. Transient elastography (Fibroscan) is widely used by clinicians. Acoustic radiation force impulse (ARFI) is an elastography technique recently integrated in clinical ultrasound systems that may provide similar diagnostic performance to transient elastography. Magnetic resonance elastography (MRE) is a new method that can be integrated to a liver MRI study, which would allow liver stiffness, steatosis, iron overload and inflammation quantification in chronic liver disease.
Objectives: 1) To compare the sensitivity of MRE and ARFI for detecting histology-determined significant fibrosis (F ≥ 2). Secondary objectives: 2) To compare the diagnostic accuracy of MRE, ARFI and Fibroscan for predicting histology-determined fibrosis stages. 3) To determine the influence of inflammation, steatosis, and iron deposition on the diagnostic accuracy of MRE, ARFI and Fibroscan for predicting fibrosis. 4) To determine thresholds optimizing sensitivity of ARFI and Fibroscan to screen patients and optimizing specificity of MRE to confirm liver fibrosis stage.
Design: This will be a cross-sectional imaging trial comparing feasibility, diagnostic and fibrosis staging accuracy of stiffness measurements by elastographic methods in 108 patients with chronic liver disease, using histopathology as the reference standard. Paired index tests (MRE, ARFI and Fibroscan) will be performed as research procedures in close temporal proximity to the reference test (liver biopsy).
Inclusion criteria: consecutive adult patients with known or suspected chronic liver disease secondary to hepatitis B virus, hepatitis C virus, or nonalcoholic fatty liver disease (NAFLD) undergoing a liver biopsy for clinical indications.
Exclusion criteria: any contraindication to MRI, refusal to participate or provide informed consent, pregnant women, any other cause of chronic liver disease than hepatitis B, hepatitis C or NAFLD.
- Conditions
- Hepatitis C, Hepatitis B, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
- Being tested
- Transient elastography, acoustic radiation force impulse, magnetic resonance elastography
- Keywords
- Chronic liver disease, Fibrosis, Elastography, Ultrasound, Magnetic resonance elastography, Diagnostic performance, Sensitivity and specificity
- Medical subject headings
- Hepatitis C, Hepatitis B, Non-alcoholic Fatty Liver Disease, Fibrosis, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transient elastography, acoustic radiation force impulse, magnetic resonance elastographyDevice
Also called Transient elastography (Fibroscan), Acoustic Radiation Force Impulse (ARFI), Magnetic Resonance Elastography (MRE)
Transient elastography (Fibroscan) Acoustic Radiation Force Impulse (ARFI) Magnetic Resonance Elastography (MRE)
| Study group | Role | What they receive |
|---|---|---|
| Hepatis C, Hepatitis B, NAFLD | All patients enrolled will undergo:
* Transient Elastography (Fibroscan)
* Acoustic Radiation Force Impulse (ARFI)
* Magnetic Resonance Elastography (MRE) Receives: Device: Transient elastography, acoustic radiation force impulse, magnetic resonance elastography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Histology-determined fibrosis stage
Measured: Within 6 weeks of elastographic methods
Secondary outcomes (5)
Fibroscan-determined liver stiffness
Measured: Within 6 weeks of liver biopsy
Acoustic Radiation Force Impulse (ARFI)-determined liver stiffness
Measured: Within 6 weeks of liver biopsy
Magnetic Resonance Elastography (MRE)-determined liver stiffness
Measured: Within 6 weeks of liver biopsy
Magnetic Resonance Imaging (MRI)-based Proton Density Fat Fraction (PDFF)
Measured: Within 6 weeks of liver biopsy
Magnetic Resonance Imaging (MRI) cine-tagging of cardiac-induced motion for staging liver fibrosis
Measured: Within 6 weeks of liver biopsy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionJun 2018
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Centre de Recherche du Centre Hospitalier de l'Université de Montréal
- Responsible party
- Sponsor
- Investigators
- An Tang, MD, MSc, Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02044523
- Sponsor's protocol ID
- CE12.062
- Acronym
- ELF
- Status last verified
- Jul 2017
- First submitted
- 20 Jan 2014
- Last updated
- 20 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Lefebvre T, Wartelle-Bladou C, Wong P, Sebastiani G, Giard JM, Castel H, Murphy-Lavallee J, Olivie D, Ilinca A, Sylvestre MP, Gilbert G, Gao ZH, Nguyen BN, Cloutier G, Tang A. Prospective comparison of transient, point shear wave, and magnetic resonance elastography for staging liver fibrosis. Eur Radiol. 2019 Dec;29(12):6477-6488. doi: 10.1007/s00330-019-06331-4. Epub 2019 Jul 5.
PubMed 31278577
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Magnetic Resonance and Ultrasound Elastography With Liver Biopsy for Noninvasive Staging of Liver Fibrosis
- ClinicalTrials.gov ID
- NCT02044523
- Acronym / sponsor ID
- ELF / CE12.062
- Conditions
- Hepatitis C, Hepatitis B, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
- Keywords
- Chronic liver disease, Fibrosis, Elastography, Ultrasound, Magnetic resonance elastography, Diagnostic performance, Sensitivity and specificity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Centre de Recherche du Centre Hospitalier de l'Université de Montréal
- Study start
- Jan 2014
- Primary completion
- Jun 2018 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 24 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Liver fibrosis is an important public health problem, with a substantial morbidity and mortality due to progression to cirrhosis and hepatocellular carcinoma. All causes of chronic liver disease may lead to fibrosis. The traditional diagnostic approach requires a biopsy for assessing the severity of liver disease prior to therapy.
However, liver biopsy has several limitations: cost, sampling error, and procedure-related morbidity and mortality. Considering the high prevalence of viral hepatitis and nonalcoholic fatty liver disease, a condition often associated with obesity and type 2 diabetes, there is an urgent need for noninvasive screening, diagnosis and monitoring strategies of chronic liver disease severity.
Our team has the expertise to investigate ultrasound-based and magnetic resonance-based elastographic methods for the noninvasive staging of liver fibrosis.
The primary objective of this cross-sectional study is to compare the sensitivity of elastographic methods for detecting histology-determined significant fibrosis.
The secondary objectives are to compare the diagnostic accuracy of these elastographic methods and the influence of potential confounders (inflammation, steatosis and iron deposition) on their diagnostic accuracy.
Detailed description
Background: Liver fibrosis is an important public health problem, with a substantial morbidity and mortality due to cirrhosis (the end stage) and hepatocellular carcinoma. All causes of chronic liver disease may lead to fibrosis. The amount of fibrosis determines the prognosis and influences the response to treatment of chronic liver disease.
Several elastographic methods have been proposed for noninvasive detection and staging of liver fibrosis. Transient elastography (Fibroscan) is widely used by clinicians. Acoustic radiation force impulse (ARFI) is an elastography technique recently integrated in clinical ultrasound systems that may provide similar diagnostic performance to transient elastography. Magnetic resonance elastography (MRE) is a new method that can be integrated to a liver MRI study, which would allow liver stiffness, steatosis, iron overload and inflammation quantification in chronic liver disease.
Objectives: 1) To compare the sensitivity of MRE and ARFI for detecting histology-determined significant fibrosis (F ≥ 2). Secondary objectives: 2) To compare the diagnostic accuracy of MRE, ARFI and Fibroscan for predicting histology-determined fibrosis stages. 3) To determine the influence of inflammation, steatosis, and iron deposition on the diagnostic accuracy of MRE, ARFI and Fibroscan for predicting fibrosis. 4) To determine thresholds optimizing sensitivity of ARFI and Fibroscan to screen patients and optimizing specificity of MRE to confirm liver fibrosis stage.
Design: This will be a cross-sectional imaging trial comparing feasibility, diagnostic and fibrosis staging accuracy of stiffness measurements by elastographic methods in 108 patients with chronic liver disease, using histopathology as the reference standard. Paired index tests (MRE, ARFI and Fibroscan) will be performed as research procedures in close temporal proximity to the reference test (liver biopsy).
Inclusion criteria: consecutive adult patients with known or suspected chronic liver disease secondary to hepatitis B virus, hepatitis C virus, or nonalcoholic fatty liver disease (NAFLD) undergoing a liver biopsy for clinical indications.
Exclusion criteria: any contraindication to MRI, refusal to participate or provide informed consent, pregnant women, any other cause of chronic liver disease than hepatitis B, hepatitis C or NAFLD.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hepatis C, Hepatitis B, NAFLD | – | Device: Transient elastography, acoustic radiation force impulse, magnetic resonance elastographyAll patients enrolled will undergo: * Transient Elastography (Fibroscan) * Acoustic Radiation Force Impulse (ARFI) * Magnetic Resonance Elastography (MRE) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The target population is adults with any of the three main causes of liver fibrosis: HBV, HCV or NASH. For the purpose of this study, we will recruit patients seen at the hepatology clinic of St-Luc Hospital, a tertiary care center.
Key inclusion criteria (4 listed)
- are adults;
- must undergo a liver biopsy as part of their clinical standard of care for suspected or known chronic liver disease caused by HBV, HCV or NASH;
- understand French or English instruction;
- Autoimmune Hepatitis
Key exclusion criteria (4 listed)
- have any contra-indication to MRI (such as claustrophobia, pacemaker, metallic clips for a neurosurgical procedure);
- are pregnant or trying to become pregnant;
- have a weight or girth preventing them from entering the MR magnet bore;
- are unable to understand or unwilling to provide written informed consent for this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transient elastography, acoustic radiation force impulse, magnetic resonance elastographyAlso: Transient elastography (Fibroscan), Acoustic Radiation Force Impulse (ARFI), Magnetic Resonance Elastography (MRE)Transient elastography (Fibroscan) Acoustic Radiation Force Impulse (ARFI) Magnetic Resonance Elastography (MRE) | Device | Hepatis C, Hepatitis B, NAFLD |
Primary outcome
Histology-determined fibrosis stage
Time frame: Within 6 weeks of elastographic methods
5 secondary outcomes
Fibroscan-determined liver stiffness
Time frame: Within 6 weeks of liver biopsy
Acoustic Radiation Force Impulse (ARFI)-determined liver stiffness
Time frame: Within 6 weeks of liver biopsy
Magnetic Resonance Elastography (MRE)-determined liver stiffness
Time frame: Within 6 weeks of liver biopsy
Magnetic Resonance Imaging (MRI)-based Proton Density Fat Fraction (PDFF)
Time frame: Within 6 weeks of liver biopsy
Magnetic Resonance Imaging (MRI) cine-tagging of cardiac-induced motion for staging liver fibrosis
Time frame: Within 6 weeks of liver biopsy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2018.
- Derived from this study: PubMed 31278577Lefebvre T, Wartelle-Bladou C, Wong P, Sebastiani G, Giard JM, Castel H, Murphy-Lavallee J, Olivie D, Ilinca A, Sylvestre MP, Gilbert G, Gao ZH, Nguyen BN, Cloutier G, Tang A. Prospective comparison of transient, point shear wave, and magnetic resonance elastography for staging liver fibrosis. Eur Radiol. 2019 Dec;29(12):6477-6488. doi: 10.1007/s00330-019-06331-4. Epub 2019 Jul 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
An Tang, MD, MSc principal investigator
Centre hospitalier de l'Université de Montréal (CHUM)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis C and Hepatitis B, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histology-determined fibrosis stage (time frame: Within 6 weeks of elastographic methods). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02044523, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2018.