Prevention of Hepatocellular Carcinoma Related to Metabolic Syndrome

预防与代谢综合征相关的肝细胞癌

基本信息

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
项目类别：
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

项目摘要

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）是美国人癌症死亡增长最快的原因。在过去的十年中，与代谢（功能障碍）相关的疾病呈流行趋势。脂肪肝病 (MAFLD) 相关的肝硬化和 HCC。 MAFLD 预计影响 10 亿人预计将成为未来 20 年 HCC 的主要原因。迫切需要制定有效的策略来减少日益增长的 HCC 负担 MAFLD 人口。该计划项目 (PP) 的总体目标是减轻 HCC- 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）以及 HCC 相关的保护因素（例如化学预防、HCC 监测）到MAFLD。我们提出三项高度综合的研究。该 PP 的核心是利用和扩大我们的多城市前瞻性 MAFLD 相关肝硬化患者队列，德克萨斯州 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、患有以下疾病的患者代谢功能障碍的代谢、放射组学和遗传标记肝硬化。我们建议对前瞻性 THCCC 的数据和生物样本进行分析由超过 5000 名肝硬化患者（以及 350-400 名 HCC 患者）组成的队列来制定一套风险评分算法）用于预测肝硬化患者患 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可降低 MAFLD 患者患 HCC 的风险。我们提出一项回顾性队列研究，使用超过 580,000 名患者的国家 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这些药物用于 THCCC 的 MAFLD 肝硬化患者。项目 3 的目标是检查预防策略的比较成本效益在MAFLD。我们将开发数学模拟模型并进行比较分析对 MAFLD 患者进行化学预防和 HCC 监测的益处与危害，以及使用 HCC 风险分层进行精准监测/化学预防我们提出了一个数据和分析核心来支持数据管理、数据协调、统计分析和基于网络的工具；生物样本和生物标志物开发核心支持 THCCC 血清和 DNA 样本的收集、处理、运输和储存队列；并为项目进行生物标志物测定，以及一个管理核心来提供项目、核心、研究者和工作人员之间的管理、沟通和协调。