Quantitative Ultrasound Techniques for Diagnosis of Nonalcoholic Steatohepatitis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 102
- 试验地点
- 2
- 主要终点
- Fibrosis stage
研究概览
简要总结
Nonalcoholic fatty liver disease is the most common liver disease in Western countries, due in large part to its association with type 2 diabetes and obesity. The more advanced form of this disease is known as nonalcoholic steatohepatitis (NASH). If left untreated, NASH can evolve to cirrhosis, the late stage of fibrosis. Once cirrhosis is established, patients are at increased risk of developing gastrointestinal bleeding, liver cancer and liver failure that may require transplantation. A liver biopsy is currently needed to diagnose the severity of fatty liver disease but this is usually not indicated in asymptomatic patients. This procedure requires the insertion of a needle inside the liver to remove a small piece of tissue for examination under microscope. Liver biopsy is an invasive procedure with a small risk of major complications such as bleeding in 0.5% of cases. It is also affected by sub-optimal sampling leading to diagnostic errors
Ultrasound is optimum for screening patients with or without symptoms because it is a safe and widely available technology to scan the whole liver. Members of our team have developed Advanced ultrasound techniques that provide unique information not possible with state-of-the-art techniques. Unlike liver biopsy, these techniques would be applicable even in asymptomatic patients because it is non-invasive. This research proposal proposes a novel approach for diagnosis of NASH and will be the first study to measure individual components of NASH (fat, inflammation and fibrosis) with quantitative ultrasound (QUS) scores. This study is timely because NASH is the second leading cause of liver transplantation in North America and is predicted to become the leading indication in the near future.
详细描述
BACKGROUND - Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in Western countries. The more advanced form, nonalcoholic steatohepatitis (NASH) may evolve to fibrosis, cirrhosis, liver failure and liver cancer. Liver biopsy is the current reference standard for diagnosis of NASH. However, its invasiveness prevent its use for large-scale screening and diagnosis. Members of our team have developed innovative quantitative ultrasound (QUS) techniques (shear wave viscoelastography and sub-resolution cellular imaging) that have a high diagnostic potential. Advantages over magnetic resonance (MR) include the ability to characterize viscosity, cellular organizations and cost-effectiveness. We hypothesize that a combination of QUS techniques offering complementary assessment of tissue characteristics will differentiate NASH from NAFLD and quantify evolving grades of liver fat, inflammation and fibrosis.
OBJECTIVES - Primary objective: 1) Determine the accuracy of QUS parameters for diagnosis of NASH. Secondary objectives: 2) Determine the diagnostic accuracy of QUS for grading histology-determined liver fat, inflammation and fibrosis. 3) Compare the diagnostic accuracy of QUS and MR techniques for liver fat quantification.
Hypotheses: We hypothesize that QUS methods, including viscoelasticity, homodyned-K parameters and attenuation parameters can characterize properties of tissues encountered in NASH (including liver fat, inflammation and fibrosis).
METHODOLOGY - Design: This will be a cross-sectional imaging trial to evaluate the diagnostic accuracy of QUS techniques in 10 non-obese volunteers and 92 patients, using histopathology as the reference standard for patients. Paired index tests QUS-based (mechanical and cellular parameters) and MR-based (mechanical parameters and relaxation times reflecting tissue content) techniques 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 NAFLD or NASH undergoing a liver biopsy for clinical indications.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Are at least 18 years old at screening;
- •Able to comprehend and willingness to provide voluntary consent;
- •Understand French or English;
- •NAFLD/NASH subjects:
- •Have a suspected or known NAFLD or NASH;
- •Must undergo a liver biopsy as part of their clinical standard of care
- •Non-NAFLD volunteers:
- •Do not have a suspected or known NAFLD or NASH
排除标准
- •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;
- •Non-NAFLD volunteers:
- •Have risk factors for developing liver steatosis (type 2 diabetes mellitus, alcohol consumption >60g of alcohol per day, lipogenic medication and body mass index >25 kg/m2);
- •Have a liver steatosis (defined as MRI-proton density fat fraction <5%);
- •NAFLD/NASH subjects:
- •Have other causes of chronic liver disease;
- •Have a liver transplant
研究组 & 干预措施
NAFLD, NASH patients
All patients enrolled will undergo:
- Acoustic Radiation Force Impulse (ARFI)
- Magnetic Resonance Elastography (MRE)
干预措施: Acoustic radiation force impulse (ARFI), magnetic resonance elastography (MRE) (Device)
Non-obese volunteers
All patients enrolled will undergo:
- Acoustic Radiation Force Impulse (ARFI)
- Magnetic Resonance Elastography (MRE)
干预措施: Acoustic radiation force impulse (ARFI), magnetic resonance elastography (MRE) (Device)
结局指标
主要结局
Fibrosis stage
时间窗: Within 6 weeks of liver biopsy
Measure of fibrosis stage using histology
次要结局
- Liver stiffness determined by MRE(Within 6 weeks of liver biopsy)
- Liver stiffness determined by ARFI(Within 6 weeks of liver biopsy)
- Magnetic Resonance Imaging (MRI)-based Proton Density Fat Fraction (PDFF)(Within 6 weeks of liver biopsy)
- Staging liver fibrosis(Within 6 weeks of liver biopsy)