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）是美国人因癌症死亡人数增长最快的原因。