Prevention of Hepatocellular Carcinoma Related to Metabolic Syndrome

预防与代谢综合征相关的肝细胞癌

• 批准号: 10657412
• 负责人: Hashem B El-Serag
• 金额: $ 161.77万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657412
• 关键词: Address; Adult; Affect; Alcoholic Liver Diseases; Algorithms; American; Benefits and Risks; Biochemical; Biological; Biological Assay; Biological Markers; Blood specimen; Cancer Etiology; Carcinoma; Cessation of life; Chemoprevention; Chemopreventive Agent; Chronic Hepatitis C; Cirrhosis; Cities; Clinical; Collaborations; Collection; Communication; DNA; Data; Data Analyses; Data Collection; Data Set; Development; Diabetes Mellitus; Epidemic; Etiology; Foundations; Functional disorder; Future; Genetic; Genetic Markers; Goals; Hepatitis B; Hepatitis C; Incidence; Individual; Institution; Knowledge; Liver; Liver Cirrhosis; Liver diseases; Malignant neoplasm of liver; Mathematical Model Simulation; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolic syndrome; Metformin; Modeling; Morbidity - disease rate; Obesity; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phenotype; Population; Practice Guidelines; Prevalence; Prevention; Prevention Research; Prevention strategy; Preventive measure; Primary carcinoma of the liver cells; Process; Prospective cohort; Protocols documentation; Randomized, Controlled Trials; Recommendation; Research; Research Personnel; Resources; Retrospective cohort study; Risk; Risk Factors; Risk Reduction; Role; Sampling; Series; Serum; Statistical Data Interpretation; Subgroup; Texas; Thiazolidinediones; Ultrasonography; United States; United States National Institutes of Health; Work; biomarker development; cohort; comorbidity; comparative; comparative cost effectiveness; comparative effectiveness; cost effectiveness; curative treatments; data harmonization; data management; design; fatty liver disease; high risk; high risk population; indexing; individual variation; individualized prevention; lipidomics; liver imaging; metabolic-associated fatty liver disease; metabolomics; mortality; novel; novel marker; personalized screening; prevent; programs; prospective; protective factors; radiomics; risk prediction; risk stratification; sample collection; surveillance strategy; trait; web-based tool

Hepatocelluar carcinoma (HCC) is the fastest growing cause of cancer deaths among Americans. In the past decade, there has been an epidemic increase in metabolic (dysfunction) associated fatty liver disease (MAFLD)-related cirrhosis and HCC. MAFLD is estimated to affect 1 billion individuals globally and is projected to become the leading cause of HCC in the next 2 decades. There is an urgent need to develop effective strategies to reduce HCC burden in the growing MAFLD population. The overall goal of the Program Project (PP) is to reduce the burden of HCC- related mortality through better understanding of contemporary risk factors (e.g., metabolic traits and biomarkers) and protective factors (e.g., chemoprevention, HCC surveillance) of HCC related to MAFLD. We propose three highly integrated studies. Central to this PP is leveraging and expanding our multicity, prospective cohort of persons with MAFLD-related cirrhosis, the Texas HCCC Consortium (THCCC) Cohort, which will serve as a resource for the proposed studies. The goal of Project 1 is to develop HCC risk stratification models based on phenotypic, metabolic, radiomic and genetic markers of metabolic dysfunction among patients with cirrhosis. We propose the analysis of data and biospecimens from the prospective THCCC cohort of >5000 patients with cirrhosis (and 350-400 incident HCC) to develop a suite of risk score algorithms) for predicting the risk of HCC among patients with cirrhosis. The goal of Project 2 is to evaluate the chemopreventive effects and potential harms of metformin, statins or glitazones in reducing the risk of HCC in individuals with MAFLD. We propose a retrospective cohort study using national VA datasets of >580,000 patients with MAFLD. We will also examine the effect of genetic markers on the chemopreventive effects of these medications in patients with MAFLD cirrhosis in THCCC. The goal of Project 3 is to examine comparative cost-effectiveness of prevention strategies in MAFLD. We will develop a mathematical simulation model and perform comparative analyses of benefits vs. harms of chemoprevention and HCC surveillance in individuals with MAFLD, and of using precision surveillance/chemoprevention using HCC risk stratification We propose a Data & Analysis Core to support data management, data harmonization, statistical analyses and web-based tools; a Biospecimen and Biomarker Development Core to support collection, processing, transport and storage of serum and DNA samples from THCCC cohort; and conduct biomarker assays for the projects, and an Administrative Core to provide management, communication and coordination among projects, Cores, investigators and staff.

肝素癌（HCC）是美国人癌症死亡最快的原因。 在过去的十年中，代谢（功能障碍）相关的流行病 脂肪肝病（MAFLD）相关的肝硬化和HCC。据估计，黑手党会影响10亿 全球个人，预计将在未来20年成为HCC的主要原因。 迫切需要制定有效的策略来减轻HCC的负担 黑手党人口。该计划项目（PP）的总体目标是减轻HCC的负担 通过更好地理解当代风险因素（例如，代谢特征），相关死亡率 与HCC相关的保护因素（例如化学预防，HCC监视）和生物标志物）和保护因素（例如 致黑手党。我们提出了三项高度综合的研究。该PP的中心是利用的， 扩大我们与黑手党相关的肝硬化的人群的众多人群，德克萨斯州 HCCC财团（THCCC）队列，将作为拟议研究的资源。 项目1的目的是基于表型开发HCC风险分层模型， 患者的代谢功能障碍的代谢，放射性和遗传标记 肝硬化。我们提出了来自前瞻性THCCC的数据和生物测量的分析 > 5000例肝硬化患者（和350-400事件HCC）的队列，以开发一套风险评分 算法）用于预测肝硬化患者中HCC的风险。 项目2的目的是评估化学预防效应和潜在危害 二甲双胍，他汀类药物或Glitazones降低了MAFLD患者的HCC风险。我们 提出了一项回顾性队列研究，使用> 580,000名患者的国家VA数据集 黑手党。我们还将检查遗传标记对化学预防作用的影响 这些药物在THCCC中患有MAFLD肝硬化的患者中。 项目3的目标是检查预防策略的比较成本效益 在黑手党。我们将开发一个数学模拟模型，并执行比较分析 益处与化学预防和HCC监视的损害对MAFLD的人以及 使用精度监视/化学预防使用HCC风险分层 我们提出了一个数据和分析核心，以支持数据管理，数据协调， 统计分析和基于Web的工具；生物测量和生物标志物发展核心 支持THCCC的血清和DNA样品的收集，加工，运输和存储 队列；并为项目进行生物标志物测定法，以及提供的行政核心 项目，核心，调查人员和员工之间的管理，沟通和协调。