Multidisciplinary approach to study of patients with Severe Alcoholic Hepatitis Undergoing Liver Transplantation
多学科方法对接受肝移植的重症酒精性肝炎患者进行研究
基本信息
- 批准号:10356010
- 负责人:
- 金额:$ 162.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAccountingAcuteAddressAdoptedAdoptionAlcohol consumptionAlcoholic HepatitisAlcoholic Liver DiseasesAnimal ModelAnimalsAntibodiesApplications GrantsAutoantibodiesBehavior TherapyBiologicalCaringCirrhosisClinicalCommunitiesCountryCritical IllnessDevelopmentDiseaseEnsureEthical AnalysisEthical IssuesEthicsExposure toFunctional disorderGuidelinesHeavy DrinkingHumanImmune systemImmunologicsIn VitroInstitutesInterventionKnowledgeLengthLifeLiverLiver RegenerationMedicalMolecularOrgan DonationsOutcomePaperPatient SelectionPatientsPerceptionPhenotypePilot ProjectsPoliciesPopulationPrognosisProgram Research Project GrantsProteinsProteomicsProtocols documentationProviderPublic OpinionResearchResourcesRisk FactorsRoleSavingsSelection CriteriaSeriesSeverity of illnessStandardizationSteroidsSuspensionsSyndromeTherapeuticTimeTissuesTransplant RecipientsTransplantationUnited StatesUnited States National Institutes of HealthWorkalcohol exposurealcohol researchbasebehavioral pharmacologycandidate selectioncohortcollaborative approachend stage liver diseaseevidence baseinsightinterdisciplinary approachliver transplantationmortalitymultidisciplinarynovelorgan allocationpatient subsetspolicy implicationpost-transplantpreventable deathproblem drinkerprospectiverecidivismresponserisk minimizationsobrietystem cellssubstance abuse treatmenttransplant centerstransplant modeltreatment strategy
项目摘要
Summary
Alcoholic liver disease is among the most common indications for liver transplant (LT), accounting for over ¼ of LTs
performed annually in the United States. Given concerns of post-transplant recidivism and also the possibility for clinical
improvement pre-transplant with abstinence, transplant centers have required 6 months of documented sobriety prior to
LT. However, a subset of patients present for medical care with severe alcoholic hepatitis (SAH), requiring urgent and
aggressive medical management. If they are unresponsive to steroid-based medical treatment, LT is the only life-saving
option. Without LT, SAH patients have a 70-80% three-month mortality, therefore a 6-month sobriety rule precludes these
patients from life-saving LT. We have demonstrated through a pilot study and the largest series in the world, that LT for
SAH provides excellent short-term survival and similar recidivism rates in comparison to LT for alcoholic cirrhotics with 6
months sobriety.
LT for SAH is rare and controversial, because at most centers, the standard 6-month sobriety period is a transplant
candidacy requirement. However, critics of the 6 month criteria emphasize that it is an arbitrary length of time and an
unreliable predictor of recidivism. In order to minimize risk to the public perception of organ donation, careful analysis of
LT selection criteria is crucial to ensure allocation to those with the greatest survival benefit and highest chance of
maintained sobriety. Appropriate candidate selection criteria, in an ethical manner, is paramount to identify select SAH
patients who would significantly benefit from LT.
In this grant proposal we will quantify outcomes and identify risk factors for poor survival after LT in SAH. We will
compare outcomes of LT in SAH patients with other end-stage liver disease patients, and determine the ethical issues and
evaluate public opinion regarding early LT in SAH patients in an effort to determine a more rational national policy.
Further, we propose to more rigorously examine recidivism in our patients post-transplant and compare differing
behavioral and pharmacologic interventions to identify best practice care. We also propose to study explanted livers from
patients undergoing transplant to characterize at the protein, antibody, and molecular level changes that may help
articulate the pathophysiology of SAH. Lastly, we seek to utilize small animal models of liver transplantation in conjunction
with alcohol exposure to answer questions about liver regeneration, stem cells, and the immune system that cannot be
answered directly from our patients. This work is now being conducted under the auspices of our newly formed “DELTA
Center” (Delivery of Early Liver Transplant for Alcoholic Hepatitis) at Johns Hopkins.
The quantification of survival benefit of LT in SAH compared to other LT recipients will provide a context for support in the
medical community for LT expansion in this population. These clinical aspects in addition to the identification of public
opinion regarding early LT for SAH will allow for advancement in the treatment of SAH patients at a national level.
摘要
酒精性肝病是肝移植(LT)最常见的适应症之一,占肝移植的四分之一以上
在美国每年演出一次。考虑到对移植后复发的担忧,以及临床上
改善移植前禁欲,移植中心要求6个月有文件记录的戒酒情况
中校。然而,一部分正在接受治疗的重型酒精性肝炎(SAH)患者需要紧急和
积极的医疗管理。如果他们对以类固醇为基础的治疗没有反应,LT是唯一的救命药物
选择。如果没有LT,SAH患者三个月的死亡率为70%-80%,因此6个月的戒酒规则排除了这些
患者来自救命的LT。我们已经通过一项试点研究和世界上最大的系列证明,LT for
在酒精性肝硬变患者中,SAH的短期存活率和复发率与LT相似,后者为6%
几个月的戒酒时间。
对于SAH的治疗是罕见的,也是有争议的,因为在大多数中心,标准的6个月戒酒期是一种移植
候选人资格要求。然而,批评6个月标准的人强调,这是一个武断的时间长度和
不可靠的累犯率预测指标。为了尽量减少公众对器官捐赠的认知风险,仔细分析
LT选择标准是确保分配给那些具有最大生存利益和最高机会的人的关键
保持清醒。以合乎道德的方式选择合适的候选人标准,对于确定选定的SAH至关重要
将从LT中显著受益的患者。
在这项赠款提案中,我们将量化结果,并确定SAH中LT术后存活率较低的风险因素。我们会
比较SAH患者和其他终末期肝病患者的肝移植结果,并确定伦理问题和
评估公众对SAH患者早期肝移植的意见,以努力确定更合理的国家政策。
此外,我们建议更严格地检查移植后患者的再犯罪率,并比较不同的
行为和药物干预,以确定最佳实践护理。我们还建议研究从
接受移植的患者在蛋白质、抗体和分子水平上的变化可能有助于
阐明蛛网膜下腔出血的病理生理学。最后,我们寻求利用小动物模型的肝移植联合
通过酒精暴露回答有关肝脏再生、干细胞和免疫系统的问题,这些问题不可能
直接从我们的病人那里得到答复。这项工作现在是在我们新成立的德尔塔航空公司的主持下进行的
约翰霍普金斯大学的“酒精性肝炎早期肝脏移植”项目。
将自发性蛛网膜下腔出血患者接受肝移植的生存益处与其他接受肝移植的患者进行比较,这将为
在这一人群中扩大LT的医学界。这些临床方面除了识别公众
关于SAH的早期LT的意见将允许在全国范围内推进SAH患者的治疗。
项目成果
期刊论文数量(0)
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ANDREW M. CAMERON其他文献
ANDREW M. CAMERON的其他文献
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{{ truncateString('ANDREW M. CAMERON', 18)}}的其他基金
Development of an Interactive Bioethics Training Module for Healthcare Providers Treating Patients Who Need Liver Transplant for Alcohol-associated Liver Disease
为治疗酒精相关性肝病需要肝移植的患者的医疗保健提供者开发交互式生物伦理学培训模块
- 批准号:
10785093 - 财政年份:2023
- 资助金额:
$ 162.12万 - 项目类别:
Multidisciplinary approach to study of patients with Severe Alcoholic Hepatitis Undergoing Liver Transplantation
多学科方法对接受肝移植的重症酒精性肝炎患者进行研究
- 批准号:
10560540 - 财政年份:2019
- 资助金额:
$ 162.12万 - 项目类别:
Project 1-Cohort and Ethical Analysis of Patients undergoing Early Liver Transplant for Severe Alcoholic Hepatitis
项目1-严重酒精性肝炎早期肝移植患者的队列和伦理分析
- 批准号:
10356013 - 财政年份:2019
- 资助金额:
$ 162.12万 - 项目类别:
Project 1-Cohort and Ethical Analysis of Patients undergoing Early Liver Transplant for Severe Alcoholic Hepatitis
项目1-严重酒精性肝炎早期肝移植患者的队列和伦理分析
- 批准号:
10560558 - 财政年份:2019
- 资助金额:
$ 162.12万 - 项目类别:
Multidisciplinary approach to study of patients with Severe Alcoholic Hepatitis Undergoing Liver Transplantation
多学科方法对接受肝移植的重症酒精性肝炎患者进行研究
- 批准号:
10093975 - 财政年份:2019
- 资助金额:
$ 162.12万 - 项目类别:
Project 1-Cohort and Ethical Analysis of Patients undergoing Early Liver Transplant for Severe Alcoholic Hepatitis
项目1-严重酒精性肝炎早期肝移植患者的队列和伦理分析
- 批准号:
10093986 - 财政年份:2019
- 资助金额:
$ 162.12万 - 项目类别:
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