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: 10410749
• 负责人: Hashem B El-Serag
• 金额: $ 156.28万
• 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/10410749
• 关键词: Address; Adult; Affect; Alcoholic Liver Diseases; Algorithms; American; Benefits and Risks; Biochemical Genetics; Biological; Biological Assay; Biological Markers; Blood specimen; Cancer Etiology; Carcinoma; Cessation of life; Chemoprevention; Chemopreventive Agent; Chronic Hepatitis C; Cirrhosis; Clinical; Collection; Communication; DNA; Data; Data Analyses; Data Collection; Data Set; Development; Diabetes Mellitus; Epidemic; Etiology; Foundations; Future; 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; Research; Research Personnel; Resources; Retrospective cohort study; Risk; Risk Factors; Role; Sampling; Series; Serum; Statistical Data Interpretation; Subgroup; Texas; Thiazolidinediones; Ultrasonography; United States; United States National Institutes of Health; Work; base; 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 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.

肝细胞癌（HCC）是美国人中增长最快的癌症死亡原因。 在过去的十年中，与糖尿病相关的代谢（功能障碍）呈流行性增加。 脂肪肝（MAFLD）相关的肝硬化和HCC。MAFLD估计影响10亿人 在全球范围内，它将成为HCC的主要病因。 迫切需要制定有效的战略，以减少肝癌的负担， MAFLD人群。计划项目（PP）的总体目标是减轻HCC的负担- 通过更好地了解当代风险因素（例如，代谢特征 和生物标志物）和保护因子（例如，化学预防、HCC监测） 关于MAFLD我们提出了三个高度综合的研究。该PP的核心是利用和 扩大我们的多城市，前瞻性队列的人与MAFLD相关的肝硬化，得克萨斯州， HCCC联盟（THCCC）队列，将作为拟议研究的资源。 项目1的目标是开发基于表型的HCC风险分层模型， 代谢障碍患者的代谢、放射组学和遗传标志物 肝硬化我们建议分析数据和生物标本从前瞻性THCCC >5000例肝硬化患者（和350-400例新发HCC）的队列，以制定一套风险评分 算法）用于预测肝硬化患者中HCC的风险。 项目2的目标是评估化学预防效果和潜在危害， 二甲双胍、他汀类药物或格列酮类药物在降低MAFLD患者HCC风险中的作用。我们 提出一项回顾性队列研究，使用超过580，000例患者的国家VA数据集， MAFLD。我们还将研究遗传标记对化学预防作用的影响， 在THCCC的MAFLD肝硬化患者中使用这些药物。 项目3的目标是审查预防战略的比较成本效益 在MAFLD。我们将建立一个数学模拟模型并进行比较分析 MAFLD患者中化学预防和HCC监测的益处与危害，以及 使用精确监测/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， 统计分析和基于网络的工具;生物标本和生物标志物开发核心 支持从THCCC收集、处理、运输和储存血清和DNA样本 队列;并为项目进行生物标志物测定，以及提供 项目、核心、调查员和工作人员之间的管理、沟通和协调。