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:10093975
- 负责人:
- 金额:$ 163.51万
- 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 RegenerationLiver diseasesMedicalMolecularOrgan DonationsOutcomePaperPatient SelectionPatientsPerceptionPhenotypePilot ProjectsPoliciesPopulationPrognosisProgram Research Project GrantsProteinsProteomicsProtocols documentationProviderPublic OpinionResearchResourcesRisk FactorsRoleSavingsSelection CriteriaSeriesSeverity of illnessStandardizationSteroidsSuspensionsSyndromeTherapeuticTimeTissuesTransplant RecipientsTransplantationUnited StatesUnited States National Institutes of HealthWorkalcohol exposurealcohol researchbasebehavioral pharmacologycandidate selectioncohortcollaborative approachevidence 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.
总结
项目成果
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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:
$ 163.51万 - 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:
$ 163.51万 - 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:
$ 163.51万 - 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:
$ 163.51万 - 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:
10356010 - 财政年份:2019
- 资助金额:
$ 163.51万 - 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:
$ 163.51万 - 项目类别:
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