Non-invasive screening of diabetics for advanced fibrosis due to NAFLD

对糖尿病患者进行 NAFLD 引起的晚期纤维化的无创筛查

• 批准号: 10392426
• 负责人: ROHIT LOOMBA
• 金额: $ 56.71万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-20 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10392426
• 关键词: Address; Adult; Affect; Age; Area; Biological Markers; Biopsy; Cessation of life; Chronic; Cirrhosis; Clinical; Cost Effectiveness Analysis; Costs and Benefits; Data; Detection; Diagnostic; Diagnostic tests; Disease; Disease Progression; Early identification; Equilibrium; Exhibits; Fatty Liver; Fatty acid glycerol esters; Fibrosis; Future; Goals; Gold; Hepatic; Image; Intervention; Knowledge; Liver; Liver Fibrosis; Longitudinal Studies; Magnetic Resonance Imaging; Modeling; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Participant; Patients; Phenotype; Pilot Projects; Population; Practice Guidelines; Prevalence; Primary carcinoma of the liver cells; Prognosis; Prospective cohort; Protons; Reference Standards; Reproducibility; Risk; Risk Factors; Serum; Subgroup; Technology; Testing; Time; Uncertainty; base; clinical practice; cohort; cost; cost effective; cost effectiveness; cost-effectiveness evaluation; density; diabetic; diagnostic accuracy; diagnostic screening; diagnostic strategy; elastography; end stage liver disease; high risk population; imaging biomarker; imaging modality; liver biopsy; liver stiffness; liver transplantation; mathematical model; mortality risk; non-alcoholic fatty liver disease; non-invasive imaging; nonalcoholic steatohepatitis; primary outcome; routine screening; screening

PROJECT SUMMARY Nonalcoholic fatty liver disease (NAFLD) affects an estimated 30% of the adult U.S. population1-3. Several studies suggest type 2 diabetes mellitus (T2DM) is a strong independent risk factor for NAFLD progression to NASH and liver fibrosis4-13 and confers an increased risk of hepatocellular carcinoma14-18. However, current AASLD NAFLD practice guidelines state routine screening for NAFLD in high-risk groups such as the T2DM population “is not advised at this time because of uncertainties surrounding diagnostic tests and treatment options, along with lack of knowledge related to long-term benefits and cost-effectiveness of screening”19. Here, we propose to use advanced magnetic resonance imaging (MRI) to study and monitor NAFLD and fibrosis in a prospective cohort of T2DM patients. Our overarching goal is to collect the necessary evidence to make an informed decision on whether screening the T2DM population for advanced fibrosis due to NAFLD is advisable and cost-effective. We will also define the best screening approach, balancing diagnostic accuracy and availability with cost. Our group has developed and clinically validated two advanced magnetic resonance imaging (MRI) modalities for non-invasive assessment of liver fat and fibrosis: MRI Proton Density Fat Fraction (MRI-PDFF) and MR Elastography (MRE). Using these advanced technologies, we will accurately phenotype T2DM patients to assess their risk of advanced fibrosis and monitor rates of NAFLD progression in this population. To achieve our goal, our specific aims are: Aim 1: Test the hypothesis that MRE and VCTE can reliably and non-invasively detect the presence of advanced fibrosis due to NAFLD in T2DM patients. To evaluate diagnostic approaches for screening the T2DM population, here we will use MRI-PDFF and MRE to accurately estimate the prevalence of NAFLD and advanced fibrosis, respectively. The primary outcome will be advanced fibrosis, as defined by MRE ≥ 3.63 kPa, with additional confirmation by liver biopsy. MR-based assessments will be used as reference standards to identify corresponding cut-off values for their transient elastography counterparts, VCTE and CAP. Aim 2: Identify risk factors and biomarkers for rapid fibrosis progression in the T2DM population To define which T2DM patients are most likely to show rapid fibrosis progression, we will longitudinally follow a subset of study participants. We hypothesize that higher liver fat content at baseline (>15.7%) associates with higher rate of liver stiffness progression in the T2DM population. We further hypothesize that those with higher liver stiffness have a greater risk of progression, as defined as MRE > 4.67 kPa, or cirrhosis. We will also explore risk factors and imaging- and serum-based biomarkers that may help identify fast progressors. Aim 3: Test the hypothesis that screening T2DM patients for advanced fibrosis is cost-effective. Here, we will identify whether, when and for which T2DM subgroups NAFLD screening benefits outweigh the risks.

项目摘要 非酒精性脂肪性肝病（NAFLD）影响估计30%的美国成年人口1 -3。几 研究表明，2型糖尿病（T2 DM）是NAFLD进展至 NASH和肝纤维化4 -13，并增加肝细胞癌的风险14 -18。但目前的 AASLD NAFLD实践指南规定了在T2 DM等高危人群中进行NAFLD的常规筛查 由于诊断测试和治疗的不确定性， 选择，沿着缺乏与筛查的长期效益和成本效益相关的知识“19.在这里， 我们建议使用先进的磁共振成像（MRI）来研究和监测非酒精性脂肪肝和纤维化。 T2 DM患者的前瞻性队列。我们的首要目标是收集必要的证据， 关于是否建议筛查T2 DM人群的NAFLD所致晚期纤维化的知情决定 并且成本效益高。我们还将确定最佳的筛查方法，平衡诊断准确性， 可用性与成本。我们的团队已经开发并临床验证了两种先进的磁共振成像技术， 用于非侵入性评估肝脏脂肪和纤维化的成像（MRI）模式：MRI质子密度脂肪分数 （MRI-PDFF）和MR弹性成像（MRE）。利用这些先进的技术，我们将准确地 T2 DM患者评估其晚期纤维化风险并监测NAFLD进展率， 人口为了实现我们的目标，我们的具体目标是： 目的1：检验MRE和VCTE可以可靠且非侵入性地检测是否存在 T2 DM患者中NAFLD导致的晚期纤维化。评估筛查的诊断方法 在T2 DM人群中，我们将使用MRI-PDFF和MRE准确估计NAFLD的患病率， 晚期纤维化。主要结局为晚期纤维化，定义为MRE ≥ 3.63 kPa， 并通过肝脏活检进一步确认。基于MR的评估将用作参考标准， 确定其瞬态弹性成像对应物VCTE和CAP的相应截止值。 目的2：确定T2 DM人群中快速纤维化进展的风险因素和生物标志物 确定哪些T2 DM患者最有可能显示快速纤维化进展，我们将纵向随访 研究参与者的子集。我们假设基线时较高的肝脏脂肪含量（>15.7%）与以下因素有关： T2 DM人群中肝硬度进展率较高。我们进一步假设， 肝硬化有更大的进展风险，定义为MRE > 4.67 kPa或肝硬化。我们还将探索 风险因素和基于影像学和血清的生物标志物，可能有助于识别快速进展者。 目的3：检验对T2 DM患者进行晚期纤维化筛查具有成本效益的假设。在这里， 我们将确定NAFLD筛查的益处是否、何时以及对哪些T2 DM亚组的益处大于风险。