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.

肝细胞癌是美国人癌症死亡增长最快的原因。 在过去的十年里，与新陈代谢(功能障碍)相关的流行病增加了 脂肪肝(MAFLD)相关的肝硬变和肝细胞癌。据估计，MAFLD将影响10亿人 预计在未来20年内将成为肝细胞癌的主要病因。 迫切需要制定有效的战略来减轻不断增长的肝癌的负担 残障人士。计划项目(PP)的总体目标是减轻肝癌的负担-- 通过更好地了解当代风险因素(例如代谢特征)来实现相关死亡率 和生物标志物)和保护因素(例如，化学预防、肝细胞癌监测) 敬MAFLD。我们提出了三项高度整合的研究。这一PP的核心是利用和 扩大我们的多城市、预期的MAFLD相关肝硬变患者队列，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的肝癌风险分层模型， 糖尿病患者代谢功能障碍的代谢、放射和遗传标志物 肝硬变。我们建议对来自未来THCCC的数据和生物谱进行分析 对5000名肝硬变患者(以及350-400例肝细胞癌)患者进行队列研究，以制定一套风险评分 算法)用于预测肝硬变患者患肝癌的风险。 项目2的目标是评估化学预防的效果和潜在的危害 二甲双胍、他汀类药物或格列酮降低MAFLD患者患肝癌风险。我们 建议使用全国VA数据集进行一项回顾性队列研究，研究对象为58万名 太棒了。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中的MAFLD肝硬变患者。 项目3的目标是审查预防战略的比较成本效益 在MAFLD。我们将开发一个数学模拟模型，并进行比较分析 对患有MAFLD的个体进行化学预防和肝细胞癌监测的益处与危害，以及 使用精确的监测/化学预防，使用肝癌风险分层 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；生物样品和生物标记物开发核心 支持从THCCC收集、处理、运输和存储血清和DNA样本 队列；并为项目进行生物标记物分析，以及一个行政核心，以提供 项目、核心、调查人员和工作人员之间的管理、沟通和协调。