Noninvasive Staging of Liver Fibrosis: MR vs Ultrasound (ELF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Information provided by (Responsible Party):
Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier:
NCT02044523
First received: January 20, 2014
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Hepatitis C
Hepatitis B
Nonalcoholic Fatty Liver Disease (NAFLD)
Nonalcoholic Steatohepatitis (NASH)
Device: Transient elastography, acoustic radiation force impulse, magnetic resonance elastography

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Comparison of Magnetic Resonance and Ultrasound Elastography With Liver Biopsy for Noninvasive Staging of Liver Fibrosis

Resource links provided by NLM:


Further study details as provided by Centre hospitalier de l'Université de Montréal (CHUM):

Primary Outcome Measures:
  • Histology-determined fibrosis stage [ Time Frame: Within 6 weeks of elastographic methods ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Fibroscan-determined liver stiffness [ Time Frame: Within 6 weeks of liver biopsy ] [ Designated as safety issue: No ]
  • Acoustic Radiation Force Impulse (ARFI)-determined liver stiffness [ Time Frame: Within 6 weeks of liver biopsy ] [ Designated as safety issue: No ]
  • Magnetic Resonance Elastography (MRE)-determined liver stiffness [ Time Frame: Within 6 weeks of liver biopsy ] [ Designated as safety issue: No ]
  • Magnetic Resonance Imaging (MRI)-based Proton Density Fat Fraction (PDFF) [ Time Frame: Within 6 weeks of liver biopsy ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Liver biopsy specimens.


Estimated Enrollment: 108
Study Start Date: January 2014
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Hepatis C, Hepatitis B, NAFLD

All patients enrolled will undergo:

  • Transient Elastography (Fibroscan)
  • Acoustic Radiation Force Impulse (ARFI)
  • Magnetic Resonance Elastography (MRE)
Device: Transient elastography, acoustic radiation force impulse, magnetic resonance elastography
Transient elastography (Fibroscan) Acoustic Radiation Force Impulse (ARFI) Magnetic Resonance Elastography (MRE)
Other Names:
  • Transient elastography (Fibroscan)
  • Acoustic Radiation Force Impulse (ARFI)
  • Magnetic Resonance Elastography (MRE)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.

Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02044523

Contacts
Contact: An Tang, MD, MSc 514-890-8000 ext 36400 duotango@gmail.com
Contact: Assia Belblidia 514-890-8000 ext 34369 assia.belblidia.chum@ssss.gouv.qc.ca

Locations
Canada, Quebec
Centre Hospitalier de l'Université de Montréal Recruiting
Montreal, Quebec, Canada, H2X 0A9
Contact: An Tang, MD, MSc    514-890-8000 ext 36400    duotango@gmail.com   
Sub-Investigator: David-Olivier Chagnon, MD         
Sub-Investigator: Damien Olivié, MD         
Sub-Investigator: Claire Wartelle-Bladou, MD         
Sub-Investigator: Guy Cloutier, PhD, Ing.         
Sub-Investigator: Jacques De Guise, PhD, ing.         
Sub-Investigator: Louis Gaboury, MD         
Sub-Investigator: Guillaume Gilbert, PhD         
Sub-Investigator: Claude Kauffmann, PhD, ing.         
Sub-Investigator: Gilles Soulez, MD, Msc         
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Canadian Institutes of Health Research (CIHR)
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Investigators
Principal Investigator: An Tang, MD, MSc Centre Hospitalier de l'Université de Montréal
  More Information

No publications provided

Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT02044523     History of Changes
Other Study ID Numbers: CE12.062
Study First Received: January 20, 2014
Last Updated: January 22, 2014
Health Authority: Canada: Ethics Review Committee
Canada: Canadian Institutes of Health Research
Canada: Health Canada

Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
Chronic liver disease
Fibrosis
Elastography
Ultrasound
Magnetic resonance elastography
Diagnostic performance
Sensitivity and specificity

Additional relevant MeSH terms:
Fatty Liver
Fibrosis
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis C
Liver Diseases
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Flaviviridae Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Pathologic Processes
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 21, 2014