Project 3: Non-invasive assessment of liver fibrosis stage and progression in obesity and diabetes: a Hispanic population study

项目 3：肥胖和糖尿病肝纤维化阶段和进展的无创评估：西班牙裔人群研究

• 批准号: 10687043
• 负责人: LAURA BERETTA
• 金额: $ 102.38万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10687043
• 关键词: Address; Adult; Advanced Development; Affect; Area; Bile Acids; Biological Assay; Central obesity; Child; Cirrhosis; Clinic; Clinical; Communities; Country; County; Data; Development; Diabetes Mellitus; Diet; Early Intervention; Enrollment; Equipment; Fatty Acids; Fibrosis; Funding; Health; Hepatic; High Prevalence; Hispanic; Hispanic Populations; Incidence; Infiltration; Joints; Ligands; Liver; Liver Fibrosis; Macrophage; Mass Spectrum Analysis; Measurement; Measures; Mediator; Modeling; Molecular; Molecular Profiling; Mus; Obesity; Obesity Epidemic; Participant; Patient Schedules; Patients; Performance; Pilot Projects; Plasma; Play; Population; Population Attributable Risks; Population Study; Prevalence; Prevention; Prevention strategy; Primary carcinoma of the liver cells; Publications; Reporting; Research; Resources; Risk; Risk Factors; Role; Serum; Signal Transduction; Site; South Texas; Staging; Study Subject; Target Populations; Texas; Tissues; United States; University of Texas M D Anderson Cancer Center; chronic liver disease; clinically significant; cohort; diabetic; elastography; gut microbiome; gut microbiota; health disparity; high risk; hispanic community; liver biopsy; liver injury; male; microbiome; molecular marker; mortality; multidisciplinary; non-alcoholic; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; participant enrollment; preventive intervention; programs; progression risk; prospective; screening; sequencing platform; simple steatosis; study population; surveillance strategy; translational goal; vibration

PROJECT 3 – SUMMARY/ASTRACT HCC incidence and mortality rates are rapidly increasing in the United States, in part due to the epidemics of obesity and diabetes. The greatest increase has been seen in Hispanics in South Texas. Our studies in the Cameron County Hispanic Cohort (CCHC) established from a community with high rates of obesity (52%) and diabetes (28%), showed that chronic liver disease is also common (42%). Non-alcoholic fatty liver disease (NAFLD), the most common liver manifestation of obesity and diabetes, ranges from simple steatosis to non- alcoholic steatohepatitis (NASH). Advanced fibrosis is the main risk factor for HCC in NAFLD patients. We first reported a 3.5% prevalence of advanced fibrosis in CCHC, with a remarkable population attributable fraction of 65% for central obesity. We then implemented liver fibrosis screening in CCHC, using vibration-controlled transient elastography (VCTE), and reported a 14% prevalence of clinically significant fibrosis (stage ≥F2). The prevalence of significant liver fibrosis reached 28% in obese and diabetic subjects. Strong associations between gut microbiota changes and progression of NAFLD to NASH and HCC, have been reported and bile acids are important mediators in this gut-liver cross-talk. Furthermore, we identified fatty acids as non-invasive markers of NAFLD activitiy and liver fibrosis in patients with NAFLD. Our long-term translational goal is to determine the contributing factors and molecular drivers of liver fibrosis in obese and diabetic Hispanics in South Texas, the community in the United States with the highest rate of HCC, and identify those at risk of progression to advanced fibrosis and therefore HCC, so preventive interventions can be implemented. We hypothesize that demographic, clinical, and molecular (microbiome features, bile acids, fatty acids) parameters are associated with liver fibrosis stages in obese Hispanics with diabetes. We hypothesize further that a model based on these parameters will predict fast fibrosis progression and thus increased risk for HCC development in these subjects. We will enroll 900 obese and diabetic CCHC subjects and 500 obese and diabetic Hispanic patients scheduled for liver biopsy at participating liver clinics. All study participants will be screened for liver fibrosis with VCTE and plasma bile acids, plasma fatty acids and gut microbiome features will be measured. Study participants identified with fibrosis ≥F2 will be followed prospectively and liver fibrosis will be again assessed by VCTE and/or liver biopsy at 36 months. In Aim 1, we will determine the performance of VCTE against liver fibrosis for fibrosis staging in the study population. We will also determine the prevalence and risk factors associated with liver fibrosis in obese and diabetic Hispanics in South Texas. In Aim 2, we will identify the molecular markers among those measured that are associated with liver fibrosis stages. In Aim 3, we will identify a model incorporating selected parameters from Aim 1 and molecular markers from Aim 2 in predicting fast liver fibrosis progression in obese Hispanics with diabetes. The impact of this project would be reduction of HCC mortality rates through early intervention and prevention.

项目3 -摘要/摘要