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: 10166841
• 负责人: ROHIT LOOMBA
• 金额: $ 54.28万
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10166841
• 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; Liver diseases; 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; elastography; high risk population; imaging biomarker; imaging modality; liver biopsy; 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.

项目概要 据估计，30% 的美国成年人患有非酒精性脂肪肝 (NAFLD)1-3。一些 研究表明 2 型糖尿病 (T2DM) 是 NAFLD 进展为一个强有力的独立危险因素 NASH 和肝纤维化4-13 并增加患肝细胞癌的风险14-18。然而，目前 AASLD NAFLD 实践指南规定了 T2DM 等高危人群的 NAFLD 常规筛查 由于诊断测试和治疗的不确定性，目前不建议人群 选项，以及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 NAFLD 和纤维化 T2DM 患者的前瞻性队列。我们的首要目标是收集必要的证据来做出 就是否建议对 T2DM 人群进行 NAFLD 导致的晚期纤维化筛查做出明智的决定 并且具有成本效益。我们还将定义最佳筛查方法，平衡诊断准确性和 可用性与成本。我们的团队开发并临床验证了两种先进的磁共振 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) 和磁共振弹性成像 (MRE)。利用这些先进技术，我们将准确地进行表型分析 T2DM 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： 目标 1：检验 MRE 和 VCTE 能够可靠且非侵入性地检测是否存在的假设 T2DM 患者因 NAFLD 导致晚期纤维化。评估筛查的诊断方法 T2DM人群，这里我们将使用MRI-PDFF和MRE来准确估计NAFLD和NAFLD的患病率 分别为晚期纤维化。主要结局为晚期纤维化，定义为 MRE ≥ 3.63 kPa， 并通过肝活检进一步确认。基于 MR 的评估将用作参考标准 确定瞬时弹性成像对应物 VCTE 和 CAP 的相应截止值。 目标 2：确定 T2DM 人群快速纤维化进展的危险因素和生物标志物 为了确定哪些 T2DM 患者最有可能出现快速纤维化进展，我们将纵向跟踪 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 T2DM 人群中肝硬度进展率较高。我们进一步假设那些具有较高 肝脏僵硬进展的风险更大，定义为 MRE > 4.67 kPa 或肝硬化。我们还将探索 危险因素以及基于成像和血清的生物标志物可能有助于识别快速进展者。 目标 3：检验筛查 T2DM 患者晚期纤维化具有成本效益的假设。这里， 我们将确定是否、何时以及针对哪些 T2DM 亚组 NAFLD 筛查的益处大于风险。