Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL)

成人至成人活体肝移植队列研究 (A2ALL)

• 批准号: 8015117
• 负责人: Gregory Thomas Everson
• 金额: $ 3.06万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015117
• 关键词: Address; Adult; Affect; Allografting; Ancillary Study; Antiviral Agents; Antiviral Therapy; Bile Acid Biosynthesis Pathway; Bile Acids; Biliary; Blood Circulation; Blood Vessels; California; Cholates; Chronic Hepatitis C; Clinic Visits; Clinical; Cohort Studies; Collection; Colorado; Complex; Complication; Coupled; Data; Data Analyses; Dose; Duct (organ) structure; Enrollment; Family; Follow-Up Studies; Gene Expression; Genes; Genetic; Genotype; Guidelines; Health; Health Status; Hepatectomy; Hepatic; Hepatic Mass; Hepatitis C; Hepatitis C virus; Incidence; Isotope Labeling; Lead; Life; Link; Liver; Liver Function Tests; Liver Regeneration; Living Donor Liver Transplantation; Living Donors; Lobectomy; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Metabolism; Methods; Morbidity - disease rate; Mutation; Natural regeneration; Nuclear Receptors; Outcome; Participant; Patients; Pennsylvania; Peptide Hydrolases; Physicians; Physiological; Polymerase; Principal Investigator; Protocols documentation; Psychological adjustment; Publications; Quality of life; Randomized; Recovery; Recurrence; Regimen; Regulation; Repeat Surgery; Research; Role; Safety; San Francisco; Scanning; Second Look Surgery; Severities; Shunt Device; Social Functioning; Social status; Spleen; Surgeon; Telephone Interviews; Time; Transplant Recipients; Transplantation; Universities; Virginia; Whole Blood; Work; base; cone-beam computed tomography; design; disability; disorder later incidence prevention; follow-up; health related quality of life; inhibitor/antagonist; interest; liquid chromatography mass spectrometry; liver function; liver imaging; liver transplantation; mortality; prevent; programs; prospective; public health relevance; reconstruction; response; retransplantation; sample collection; single photon emission computed tomography; stable isotope; ursodeoxycholate

DESCRIPTION (provided by applicant): Our project addresses key issues in adult-to-adult living donor liver transplantation (LDLT). The Main Trial is an extension of the ongoing A2ALL Study - our program is an active participant and the leading enroller of patients to this trial. The current application indicates that we intend to continue to participate, accrue, and enroll patients to the trial. In the Main Trial, we will compare outcomes of LDLT recipients to the outcomes of contemporaneously studied patients undergoing deceased donor liver transplantation (DDLT). Also, in this Trial, we will conduct longitudinal long-term assessment of donors and donor controls - for the purpose of assessing the impact of donor hepatectomy and living donation on subsequent health, quality of life, and psycho-social function of donors. We propose to continue the LADR-A2ALL protocol for pre-transplant antiviral treatment of patients with chronic hepatitis C in order to prevent recurrence of hepatitis C in the allograft post-transplant. However, virologic responses in patients infected with genotype 1 HCV are inadequate to boost response in these patients and increase the efficacy of LADR-A2ALL we propose the addition of strategically-targeted-antiviral-therapies against hepatitis C (STAT-C). We also propose to continue the study of return of hepatic function in donors after right lobectomy. In our modified protocol we specifically focus on volumetric studies of liver and spleen, SPECT liver-spleen scan, and dual-isotope-labeled cholate clearances and cholate shunt to assess the physiologic changes after hepatectomy. Two ancillary studies will focus on the long-term outcomes of donors and biliary complications in recipients of LDLT. A key concern of physicians, surgeons, patients and families is whether any aspect of donor health, function, psychological adjustment, or social status is affected by LDLT. Our study will use a combination of clinic visits and assessments coupled with telephone interviews to define donor status over 2 years post-hepatectomy. Recent publications and our own analyses suggest that biliary complications are more common and more severe in LDLT recipients. In our ancillary study of biliary complications, we will compare and contrast biliary complications and outcomes between LDLT and DDLT recipients. PUBLIC HEALTH RELEVANCE: The Colorado Transplant Center aims to define a number of key issues in LDLT - long-term outcomes of LDLT, compared to DDLT, efficacy and safety of pre-transplant antiviral therapy, changes in donor hepatic mass and hepatic function after right lobectomy, long-term followup of donors and matched potential-donor controls, and incidence and severity of biliary complications after LDLT. Methods will include CT or MRI measurement of liver volume. SPECT liver-spleen scan, stable isotopes, and LC/MS.

描述（由申请人提供）：我们的项目解决了成人到成年的供体肝移植（LDLT）中的关键问题。主要试验是正在进行的A2ALL研究的扩展 - 我们的计划是活跃的参与者，并且是该试验的患者的领先入学者。当前的申请表明，我们打算继续参与，累积并招募患者参加试验。在主要试验中，我们将比较LDLT接受者的结果与正在研究已故供体肝移植（DDLT）的同时研究的患者的结果。此外，在这项试验中，我们将对捐助者和捐助者控制措施进行纵向长期评估 - 目的是评估供体肝切除术和生活捐赠对随后的健康，生活质量和捐助者心理社会功能的影响。我们建议继续采用LADR-A2ALL方案，用于对慢性丙型肝炎患者的移植前抗病毒治疗，以防止同种异体移植后移植后的丙型肝炎复发。然而，感染1 HCV的患者的病毒学反应不足以提高这些患者的反应，并提高LADR-A2ALL的疗效，我们建议对抗丙型肝炎（Stat-c）的策略性靶向抗病毒 - 抗病毒 - 疗法（Stat-C）。我们还建议在正确的叶切除术后继续研究供体中肝功能的回报。在我们的修改方案中，我们专门专门研究肝脏和脾脏，Spect Liver-Spleen扫描以及双异位标记的卫生间清除率和巧克力分流术，以评估肝切除术后的生理变化。两项辅助研究将侧重于LDLT接受者的捐助者和胆道并发症的长期结局。医师，外科医生，患者和家庭的关键关注点是捐助者健康，功能，心理调整或社会地位的任何方面是否受LDLT的影响。我们的研究将结合诊所就诊和评估以及电话访谈，以在羊角切除术后2年内定义供体状态。最近的出版物和我们自己的分析表明，LDLT接受者的胆道并发症更为普遍，更严重。在我们对胆道并发症的辅助研究中，我们将比较和对比LDLT和DDLT受体之间的胆道并发症以及结果。 公共卫生相关性：科罗拉多州移植中心旨在定义LDLT中的许多关键问题 - LDLT的长期结局，与DDLT相比，与DDLT相比，前移植前抗病毒疗法的功效和安全性，供体肝质量和肝脏切除术后的供体肝和肝功能的变化，供应术后的供应术和匹配的长期后续性，以及临时的供应剂，以及对匹配的疾病，急诊和donor偶然性的疾病，急诊和donor的疾病，急诊和donor的疾病，急诊和donor的疾病，急诊和donor的疾病，急诊和donor的疾病。 ldlt。方法将包括肝脏体积的CT或MRI测量。 Spect Liver-Spleen扫描，稳定的同位素和LC/MS。