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.

项目摘要 非酒精性脂肪肝疾病（NAFLD）估计有30％的美国人口1-3 研究表明2型糖尿病（T2DM）是NAFLD计划的强大独立风险因素 NASH和肝纤维化为4-13，并赋予肝细胞癌14-18的风险 AASLD NAFLD实践指南州的常规屏幕屏幕筛查NAFLD高 人口“目前尚未建议在不确定的情况下不确定的茶口测试和tereatment的不确定性。 选择，以及缺乏与长期收益和筛查成本效益有关的知识” 19。 我们建议使用高级磁共振成像（MRI）研究和监测A中的NAFLD和Fibros T2DM患者的前瞻性队列。我们的总体目标是收集必要的证据 建议筛查T2DM人群是否为NAFLD引起的高级纤维化进行筛查的明智决定。 和成本效益。 成本的可用性。 对肝脂肪和纤维化的非侵入性评估的成像（MRI）方式：MRI质子密度分数 （MRI-PDFF）和MR ElastographH（MRE）。 T2DM患者评估他们的晚期纤维化风险和监测NAFLD进展的速率 人口实现我们的目标，我们的具体目标是： AIM 1：检验MRE和VCTE可以可靠且非侵入性检测的假设 T2DM患者NAFLD引起的晚期纤维化。 T2DM人口，在这里我们将使用MRI-PDFF和MRE准确估计NAFLD和 晚期FIROSIS分别是由MRE 3.63 kPa定义的晚期纤维化 通过肝活检的其他确认。 确定频率弹力射击的corpong截止值，VCTE和CAMP。 目标2：确定T2DM种群快速纤维化进展的危险因素和生物标志物 定义哪些T2DM患者最有可能显示快速纤维化进展，我们将纵向遵循 研究参与者的子集。 T2DM种群的肝脏刚度进展较高。 肝僵硬的进展风险更大 风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的进步者。 AIM 3：测试筛查T2DM患者晚期纤维化的假设具有成本效益。 我们将确定T2DM子组是否，何时及以上的NAFLD筛查优势大于风险。