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.

项目概要 美国早期肝移植联盟-前瞻性酒精相关肝病队列 评估（ACCELERATE-PACE）研究是一项针对严重酗酒患者的纵向队列研究 该队列利用早期肝移植（ELT）评估相关肝病（ALD）。 ACCELERATE 联盟拥有 4 个连接的 R01 和位于南部/东南部、中部地区的 5 个额外招募地点 大西洋、中西部和西部，并将完善和确定选择和管理的最佳实践 严重 ALD 患者在整个护理过程中考虑接受 ELT 是目前最常见的情况。 美国肝移植 (LT) 的指征 历史上，肝移植中心要求至少 6 个月饮酒 在 LT 转诊和评估之前戒酒，尽管支持最短清醒时间的经验证据是 ELT（定义为禁欲 6 个月前的 LT）越来越多地进行，但进行了大量的实践。 对于最佳 ELT 候选者的选择尚未达成共识，并且选择标准差异很大。 由于 ELT 对肝脏的潜在影响，导致获得救生护理方面的差异也存在争议。 禁欲的再补偿，这将消除对 LT 的需要 - 准确预测再补偿 有潜力提高器官效用和酒精使用功效的详细评估。 基于 LT 前心理社会因素的疾病治疗和改善的风险评分，以预测重新酗酒 需要使用来完善选择标准、优化 LT 后护理并有效治疗 AUD。 ELT 后的中期生存率非常好，但 LT 后并发症的发生率和预测因素 为了填补这些关键知识空白，我们将注册并前瞻性地关注 770 ELT。 为期 3 年，在 9 个社会人口多样化的中心对候选人和 270 名 ELT 接受者进行了培训。 目标将：(i) 告知 ELT 选择标准并调查 ELT 评估中潜在的偏差来源和 接受 ELT 的医疗保健差异；(ii) 制定无 LT 生存和补偿的风险预测评分； (iii) 确定针对严重 ALD 患者酒精使用障碍的有效治疗方法（医学、行为） ELT 后；(iv) 评估 ELT 候选者和接受者的临床结果，包括死亡率、 移植、LT 后并发症（例如癌症、心血管事件、移植物排斥/失败）以及移植质量 一个全面的数据存储库将包括社会人口学、临床、地理空间、心理社会、 行为和患者报告的结果变量 LT 文件、清单、选择会议的记录、 对 LT 程序的直接观察和临床医生访谈将确定候选者的最佳实践和陷阱 选择血液、尿液、外植体/供体组织、LT 前后肝组织、外周血的生物储存库。 单核细胞和横截面放射成像将为未来的辅助研究提供信息。