4/4-American Consortium of Early Liver Transplantation-Prospective Alcohol-associated liver disease Cohort Evaluation (ACCELERATE-PACE)

4/4-美国早期肝移植联盟-前瞻性酒精相关性肝病队列评估（ACCELERATE-PACE）

• 批准号: 10711018
• 负责人: Rafik MARK GHOBRIAL
• 金额: $ 32.48万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2030-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711018
• 关键词: Abstinence; Acceleration; Accounting; Acute; Address; Adult; Alcohol consumption; Alcoholic Hepatitis; Alcoholic Liver Diseases; American; Ancillary Study; Behavior Therapy; Behavioral; Blood; Cardiovascular system; Caring; Cessation of life; Chronic; Cirrhosis; Clinical; Clinical Pathways; Consensus; Continuity of Patient Care; Data; Effectiveness; Eligibility Determination; Enrollment; Evaluation; Event; Exclusion; Failure; Future; Geography; Graft Rejection; Health; Health Status; Heavy Drinking; Hepatitis; Heterogeneity; Hospital Costs; Hospitalization; Incidence; Individual; Interview; Knowledge; Life; Link; Liver; Liver Failure; Liver diseases; Longitudinal cohort; Malignant Neoplasms; Medical; Mental Health; Methods; Midwestern United States; Modeling; Multicenter Studies; Natural History; Organ; Outcome; Patient Outcomes Assessments; Patient Selection; Patient-Focused Outcomes; Patients; Peripheral Blood Mononuclear Cell; Pharmacotherapy; Phenotype; Policies; Procedures; Process; Prognosis; Prognostic Factor; Psychosocial Factor; Quality of life; Risk; Sample Size; Selection Criteria; Site; Social support; Sodium Chloride; Source; Standardization; Substance Use Disorder; Systematic Bias; Tissue Donors; Tissues; Transplant Recipients; Transplantation; Transplanted Liver Complication; Urine; Waiting Lists; access disparities; addiction; alcohol abstinence; alcohol use disorder; biobank; candidate selection; clinical predictors; cohort; comorbidity; data repository; disorder control; drinking; effective therapy; efficacy evaluation; end stage liver disease; experience; graft function; health care disparity; high risk; implicit bias; improved; liver transplantation; medication-assisted treatment; meetings; mortality; mortality risk; multilevel analysis; organ allocation; prevent; prolonged abstinence; prospective; psychosocial; radiological imaging; recruit; risk prediction; safety assessment; sobriety; social health determinants; sociodemographics; transplant centers; treatment program

PROJECT SUMMARY The American Consortium of Early Liver Transplantation-Prospective Alcohol-associated liver disease Cohort Evaluation (ACCELERATE-PACE) study is a prospective longitudinal cohort of patients with severe alcohol- associated liver disease (ALD) evaluated for early liver transplantation (ELT). The cohort leverages the ACCELERATE consortium with 4-linked R01s and 5 additional recruitment sites in the South/Southeast, Mid- Atlantic, Midwest, and West, and will refine and identify best practices in the selection and management of patients with severe ALD considered for ELT across their continuum of care. ALD is now the most common indication for liver transplantation (LT) in the U.S. Historically, LT centers required at least 6 months of alcohol abstinence before LT referral and evaluation, though empiric evidence to support minimum sobriety periods was limited. ELT, defined as LT before 6 months of abstinence, is increasingly performed but with significant practice variability. There is no consensus on optimal ELT candidate selection, and selection criteria vary widely, contributing to disparities in access to lifesaving care. ELT is also controversial due to the potential for liver recompensation with abstinence, which would obviate the need for LT—accurate prediction of recompensation has the potential to increase organ utility and stewardship. Detailed evaluation of the efficacy of alcohol use disorder treatments and improved risk scores based on pre-LT psychosocial factors to predict return to alcohol use are needed to refine selection criteria, optimize post-LT care, and effectively treat AUD. Short- and intermediate-term survival after ELT is excellent, but the incidence and predictors of post-LT complications are poorly defined. To fill these key knowledge gaps, we will enroll and prospectively follow 770 ELT candidates and 270 ELT recipients for 3 years at 9 socio-demographically diverse centers. The proposed Aims will: (i) inform ELT selection criteria and investigate potential sources of bias in ELT evaluation and healthcare disparities in ELT access; (ii) develop risk prediction scores for LT-free survival and recompensation; (iii) identify effective treatments (medical, behavioral) for alcohol use disorder among patients with severe ALD and post-ELT; (iv) evaluate clinical outcomes among ELT candidates and recipients, including mortality, transplantation, post-LT complications (e.g. cancer, cardiovascular events, graft rejection/failure), and quality of life. A comprehensive data repository will include sociodemographic, clinical, geospatial, psychosocial, behavioral, and patient-reported outcome variables. LT documents, checklists, recordings of selection meetings, direct observations of LT procedures, and clinician interviews will identify best practices and pitfalls in candidate selection. A biorepository of blood, urine, explant/donor tissue, pre- and post-LT liver tissue, peripheral blood mononuclear cells, and cross-sectional radiologic imaging will inform future ancillary studies.

项目摘要 美国早期肝移植 - 培养酒精相关的肝病队列的美国财团 评估（加速速度）研究是严重酒精患者的前瞻性纵向队列 评估早期肝移植（ELT）的相关肝病（ALD）。该队列利用 在南部/东南部，中部/地区，有4个连接的R01和5个额外招聘地点加速联盟 大西洋，中西部和西部，将完善和确定在选择和管理方面的最佳实践 严重ALD的患者在继续护理中考虑了ELT。 ALD现在是最常见的 历史上，美国肝移植（LT）的指示，LT中心至少需要6个月的酒精 LT推荐和评估之前的禁欲，尽管经验证据支持最低清醒时期 有限的。 ELT被定义为戒酒6个月之前的LT，越来越多地执行，但具有重要的实践 可变性。在最佳ELT候选选择方面尚无共识，而选择标准差异很大， 导致获得救生护理的差异。由于肝脏的潜力，ELT也引起了争议 与禁欲的补偿，这将消除对LT的需求 - 准确预测 有可能增加器官实用性和管理。详细评估饮酒效率 基于前LT心理社会因素预测酒精恢复的疾病治疗和改善风险评分 需要使用来完善选择标准，优化LT护理并有效治疗AUD。短 - ELT后的中期生存期非常好，但是LT后并发症的事件和预测因素是 定义不佳。为了填补这些关键知识空白，我们将注册并前瞻性遵循770 ELT 候选人和270名ELT接收者在9个社会人口统计学上的中心有3年。提议 目标将：（i）通知ELT选择标准，并调查ELT评估中的潜在偏见来源 ELT访问中的医疗保健分销； （ii）无LT生存和复位的发展风险预测评分； （iii）确定严重ALD患者中饮酒障碍的有效治疗（医学，行为） 和后; （iv）评估ELT候选人和接受者之间的临床结果，包括死亡率， 移植，LT后并发症（例如癌症，心血管事件，移植拒绝/失败）和质量 生活。全面的数据存储库将包括社会人口统计学，临床，地理空间，社会心理， 行为和患者报告的结果变量。 LT文档，清单，录音会议的录音， 直接观察LT程序和临床访谈将确定候选人的最佳实践和陷阱 选择。血液，尿液，外植体/供体组织，前后肝组织，外周血液的生物措施 单核细胞和横截面放射学成像将为未来的辅助研究提供信息。