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.

项目总结 非酒精性脂肪性肝病(NAFLD)影响了大约30%的美国成年人1-3。几个 研究表明2型糖尿病(T2 DM)是NAFLD进展为 NASH和肝纤维化4-13，并增加患肝细胞癌的风险14-18。但是，当前 AASLD NAFLD实践指南规定了T2 DM等高危人群NAFLD的常规筛查 由于围绕诊断测试和治疗的不确定性，目前不建议使用“人群” 备选办法，以及缺乏与筛查的长期效益和成本效益有关的知识“19. 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 T2 DM患者的前瞻性队列研究。我们的首要目标是收集必要的证据，以便 关于对T2 DM人群进行NAFLD引起的晚期纤维化筛查是否可取的知情决定 而且性价比高。我们还将定义最佳筛查方法，平衡诊断准确性和 有成本的可用性。我们的团队已经开发出并在临床上验证了两种先进的磁共振 无创性评估肝脏脂肪和纤维化的成像(MRI)方法：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，我们将准确地进行表型 T2 DM患者评估其晚期纤维化的风险并监测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：验证MRE和VCTE可以可靠和非侵入性地检测到 2型糖尿病患者非酒精性脂肪肝所致的晚期纤维化评估筛查疾病的诊断方法 在这里，我们将使用MRI-PDFF和MRE来准确地估计NAFLD和 分别为晚期纤维化。根据MRE≥3.63kpa的定义，主要结果将是晚期纤维化， 并通过肝脏活检进行进一步确认。基于MR的评估将被用作参考标准 确定对应的瞬时弹性图对应的截止值VCTE和CAP。 目标2：确定T2 DM人群中快速纤维化进展的危险因素和生物标记物 定义哪些T2 DM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(15.7%)时较高的肝脏脂肪含量与 T2 DM人群中肝脏僵硬进展率较高。我们进一步假设，那些拥有更高 肝脏僵硬有更大的进展风险，定义为MRE&GT；4.67kpa，或肝硬变。我们还将探索 风险因素和基于成像和血清的生物标记物，可能有助于识别进展快的人。 目的3：验证对T2 DM患者进行晚期纤维化筛查具有成本效益的假设。这里, 我们将确定NAFLD筛查的益处是否大于风险，以及何时以及对哪些T2 DM亚组。