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Noninvasive Staging of Liver Fibrosis: MR vs Ultrasound

Completed
Conditions
Hepatitis C
Nonalcoholic Fatty Liver Disease (NAFLD)
Nonalcoholic Steatohepatitis (NASH)
Hepatitis B
Interventions
Device: Transient elastography, acoustic radiation force impulse, magnetic resonance elastography
Registration Number
NCT02044523
Lead Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Brief 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. 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
108
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;
  • Autoimmune Hepatitis
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Hepatis C, Hepatitis B, NAFLDTransient elastography, acoustic radiation force impulse, magnetic resonance elastographyAll patients enrolled will undergo: * Transient Elastography (Fibroscan) * Acoustic Radiation Force Impulse (ARFI) * Magnetic Resonance Elastography (MRE)
Primary Outcome Measures
NameTimeMethod
Histology-determined fibrosis stageWithin 6 weeks of elastographic methods
Secondary Outcome Measures
NameTimeMethod
Acoustic Radiation Force Impulse (ARFI)-determined liver stiffnessWithin 6 weeks of liver biopsy
Fibroscan-determined liver stiffnessWithin 6 weeks of liver biopsy
Magnetic Resonance Elastography (MRE)-determined liver stiffnessWithin 6 weeks of liver biopsy
Magnetic Resonance Imaging (MRI)-based Proton Density Fat Fraction (PDFF)Within 6 weeks of liver biopsy
Magnetic Resonance Imaging (MRI) cine-tagging of cardiac-induced motion for staging liver fibrosisWithin 6 weeks of liver biopsy

Trial Locations

Locations (1)

Centre Hospitalier de l'Université de Montréal

🇨🇦

Montreal, Quebec, Canada

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