1/4-American Consortium of Early Liver Transplantation-Prospective Alcohol-associated liver disease Cohort Evaluation (ACCELERATE-PACE)

1/4-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: 10711811
• 负责人: NORAH A. TERRAULT
• 金额: $ 57.75万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 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/10711811
• 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; 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; Neighborhoods; 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; Safety; 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; community-level factor; comorbidity; data repository; deprivation; disorder control; drinking; effective therapy; effectiveness evaluation; 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; 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 美国早期肝移植联盟-前瞻性酒精相关性肝病队列研究 评估（ACCELERATE-PACE）研究是一项前瞻性纵向队列研究， 评估早期肝移植（ELT）的相关肝病（ALD）。队列利用 ACCELERATE联盟与4个相连的R 01和5个额外的招募地点在南部/东南部，中部和南部， 大西洋，中西部和西部，并将完善和确定在选择和管理的最佳做法， 考虑在其连续护理中进行ELT的重度ALD患者。ALD现在是最常见的 在美国，肝移植（LT）的适应症历史上，LT中心需要至少6个月的酒精 在LT转诊和评估之前禁欲，尽管支持最低清醒期的经验证据是 有限公司ELT，定义为禁欲6个月前的LT，越来越多地进行，但有重要的实践 可变性对于最佳的英语候选人选择没有共识，选择标准也千差万别， 造成在获得救生护理方面的差距。ELT也是有争议的，因为肝脏的潜力 再补偿与禁欲，这将不需要LT准确预测再补偿 有可能增加器官的利用和管理。详细评估酒精使用的功效 基于LT前心理社会因素的疾病治疗和改善的风险评分，以预测酒精回归 需要使用来完善选择标准，优化LT后护理，并有效治疗AUD。短期和 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 定义不好。为了填补这些关键的知识空白，我们将招募并前瞻性地遵循770 ELT 候选人和270名ELT接受者在9个社会人口多样化中心进行了为期3年的培训。拟议 目的是：（i）告知ELT选择标准，并调查ELT评估中的潜在偏倚来源， ELT获得的医疗差异;（ii）制定无LT生存和再补偿的风险预测评分; (iii)确定严重ALD患者酒精使用障碍的有效治疗（药物，行为） （iv）评估ELT候选人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）和 生活一个全面的数据库将包括社会人口、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、甄选会议录音， LT程序的直接观察和临床医生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、LT前后肝组织、外周血的生物储存库 单核细胞和横断面放射成像将为未来的辅助研究提供信息。