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.

项目总结 美国早期肝移植联合会--前瞻性酒精相关性肝病队列 评估(Accelerate-Pace)研究是对重度酒精患者的前瞻性纵向队列研究。 对早期肝移植(ELT)的相关性肝病(ALD)进行评估。这群人利用 通过在南部/东南部、中部和南部的4个链接R01和5个额外的招聘站点加速联盟- 大西洋、中西部和西部，并将完善和确定在选择和管理 重度ALD患者考虑在整个护理过程中进行ELT。ALD现在是最常见的 美国肝移植的适应症历史上，肝移植中心至少需要6个月的酒精 在LT转诊和评估之前戒酒，尽管支持最低戒酒期的经验证据是 有限的。ELT，定义为禁欲6个月前的LT，越来越多地进行，但也有大量的练习 可变性。关于最佳英语考试考生的选择没有达成共识，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，因为潜在的肝脏 通过禁欲进行重新补偿，这将消除对重新补偿的准确预测的需要 具有提高器官效用和管理能力的潜力。酒精使用效果的详细评估 基于LT前心理社会因素的障碍治疗和改善的风险评分预测酒精回归 需要用来完善选择标准，优化LT后护理，并有效治疗AUD。简略-和 ELT后的中期存活率很好，但LT后并发症的发生率和预测因素是 定义不明确。为了填补这些关键的知识空白，我们将注册并预期遵循770英语考试 考生和270名英语教学获得者在9个社会人口统计不同的中心工作3年。建议数 AIMS将：(I)告知英语教学选择标准，并调查英语教学评估和评估中潜在的偏见来源 ELT获取方面的医疗差异；(Ii)制定无LT生存和再补偿的风险预测分数； (Iii)确定对严重ALD患者的酒精使用障碍的有效治疗(医疗、行为) 评估ELT考生和受试者的临床结果，包括死亡率， 移植、移植后并发症(如癌症、心血管事件、移植排斥/失败)和移植质量 生活。一个全面的数据储存库将包括社会人口、临床、地理空间、心理社会、 行为和患者报告的结果变量。信息技术文件、核对表、遴选会议的录音、 对肝移植程序的直接观察和临床医生面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、肝移植前后、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。