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Precision Risk Stratification and Screening for HCC among Patients with Cirrhosis in the United States

美国肝硬化患者的 HCC 精准风险分层和筛查

基本信息

批准号：
10477966
负责人：
Amit Singal
金额：
$ 71.89万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-14 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10477966
关键词：
Abdomen Biological Markers Blinded Blood Body mass index Cause of Death Center for Translational Science Activities Characteristics Cirrhosis Cohort Studies Complement Data Data Set Detection Diagnosis Early Detection Research Network Early Diagnosis Etiology Evaluation Funding Goals Heterogeneity Image Individual Liver diseases Magnetic Resonance Imaging Michigan Modeling Molecular Profiling Patients Performance Primary carcinoma of the liver cells Professional Organizations Prognosis Prospective cohort Protocols documentation Public Health Quality-Adjusted Life Years Risk Risk Factors Role Serum Severities Severity of illness Subgroup Testing Texas United States Universities alpha-Fetoproteins base biomarker panel biomarker performance case control clinical risk cohort comparative cost effectiveness compare effectiveness contrast enhanced cost effective cost effectiveness curative treatments design early detection biomarkers effectiveness testing high risk imaging biomarker improved individual patient liver cancer model models and simulation mortality novel patient population performance tests personalized screening precision medicine prospective risk stratification sample collection screening sex standard of care tumor ultrasound

项目摘要

PROJECT SUMMARY / ABSTRACT Hepatocellular carcinoma (HCC)-related mortality in the U.S. is rapidly rising. Given the association between early detection and improved survival, screening using ultrasound +/- a serum biomarker, alpha fetoprotein (AFP), is recommended in at-risk individuals, including all patients with cirrhosis. However, most HCC patients are diagnosed at a late stage due to limitations in this strategy. Specifically, the strategy of ultrasound and AFP in all cirrhosis patients is inadequate because it ignores: 1) heterogeneity in risk between patients; 2) the poor accuracy of screening tests; and 3) the poor reliability of screening test performance between patients. The current “one-size-fits-all” approach to HCC screening leads to over-screening of low-risk cirrhosis patients and under-screening of high-risk patients, diluting the overall value of HCC screening. Our proposal's goal is to develop and evaluate a precision screening strategy for early stage HCC in patients with cirrhosis that matches the best screening tests to individual risk and screening test performance. We will leverage five patient populations (4 prospective cohorts and one case-control dataset) with a total of >6000 cirrhosis patients to evaluate and compare biomarker- and imaging-based models for HCC risk stratification and early detection. Specifically, we propose to: Aim 1: Validate and compare the performance of two risk stratification models to stratify cirrhosis patients with low-, intermediate- and high-risk of developing HCC Aim 2: Evaluate the performance of an abbreviated MRI protocol +/- serum biomarkers (including AFP, AFP- L3, and DCP) vs. ultrasound +/- serum biomarkers for early HCC detection in patients with cirrhosis Aim 3: Compare the cost effectiveness, using micro-simulation modeling, of a tailored screening strategy based on individual HCC risk and expected screening test performance to the current standard strategy of ultrasound and AFP in all patients with cirrhosis Our proposal leverages 5 distinct patient populations with >6000 cirrhosis patients, to compare biomarker- and imaging-based models for HCC risk stratification and early detection. We use these data to compare the effectiveness of a tailored screening strategy to the current strategy of ultrasound and AFP for all patients using micro-simulation modeling. Tailoring HCC screening efforts to individual risk and screening test performance moves beyond the current “one-size-fits-all” strategy and aligns HCC screening with the principles of precision medicine. Our proposed HCC screening strategy would maximize screening benefits and minimize screening harms for each patient, thereby optimizing overall HCC screening value in the United States. 2

项目总结/摘要在美国，肝细胞癌（HCC）相关的死亡率正在迅速上升。考虑到早期检测和提高生存率，使用超声筛查+/-血清生物标志物，甲胎蛋白 (AFP)，推荐用于高危人群，包括所有肝硬化患者。然而，大多数HCC患者由于这种策略的局限性，在晚期才被诊断出来。具体而言，超声和AFP的策略在所有肝硬化患者中，这是不够的，因为它忽略了：1）患者之间风险的异质性; 2）穷人筛查试验的准确性;和3）患者之间筛查试验表现的可靠性差。的目前“一刀切”的HCC筛查方法导致低风险肝硬化患者的过度筛查，高风险患者的筛查不足，削弱了HCC筛查的整体价值。我们的建议的目标是开发和评估一种精确的早期肝癌筛查策略肝硬化患者的最佳筛查测试与个人风险和筛查测试性能相匹配。我们将利用5个患者人群（4个前瞻性队列和1个病例对照数据集），总计>6000 肝硬化患者评估和比较用于HCC风险分层的基于生物标志物和成像的模型及早发现。具体而言，我们建议：目的1：验证并比较两种风险分层模型对肝硬化患者进行分层的性能，发生HCC的低、中、高风险目的2：评价简化MRI方案+/-血清生物标志物（包括AFP、AFP- L3和DCP）与超声+/-血清生物标志物在肝硬化患者早期HCC检测中的比较目标3：使用微观模拟建模，比较定制筛选策略的成本效益根据个体HCC风险和当前标准策略的预期筛查测试性能，所有肝硬化患者的超声和AFP 我们的建议利用5个不同的患者人群，其中>6000名肝硬化患者，比较生物标志物和基于成像的HCC风险分层和早期检测模型。我们使用这些数据来比较针对所有患者的超声和AFP当前策略的定制筛查策略的有效性使用微观模拟建模。根据个人风险和筛查测试定制肝癌筛查工作绩效超越了目前的“一刀切”战略，并使HCC筛选符合以下原则精准医疗的一部分。我们提出的HCC筛查策略将最大限度地提高筛查益处，筛查对每个患者的危害，从而优化美国的整体HCC筛查价值。 2

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease.

DOI：
10.3350/cmh.2022.0247
发表时间：
2023-02
期刊：
CLINICAL AND MOLECULAR HEPATOLOGY
影响因子：
8.9
作者：
El Dahan, Karim Seif;Daher, Darine;Singal, Amit G.
通讯作者：
Singal, Amit G.

Hepatocellular Carcinoma Surveillance Patterns and Outcomes in Patients With Cirrhosis.

肝硬化患者的肝细胞癌监测模式和结果。

DOI：
10.1016/j.cgh.2023.08.003
发表时间：
2024
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
0
作者：
Daher,Darine;SeifElDahan,Karim;Cano,Alva;Gonzales,Michael;Ransom,Crystal;Jaurez,Erik;Carranza,Osiris;Quirk,Lisa;Morgan,Todd;Gopal,Purva;Patel,MadhukarS;Lieber,Sarah;Louissaint,Jeremy;Cotter,ThomasG;VanWagner,LisaB;Yang,
通讯作者：
Yang,

Reinforcement learning evaluation of treatment policies for patients with hepatitis C virus.