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）：我们的项目解决成人对成人活体肝移植（LDLT）的关键问题。主要试验是正在进行的 A2ALL 研究的延伸 - 我们的计划是该试验的积极参与者和主要患者招募者。目前的申请表明我们打算继续参与、招募和招募患者参加试验。在主要试验中，我们将比较 LDLT 接受者的结果与同时研究的接受死者供体肝移植 (DDLT) 的患者的结果。此外，在本试验中，我们将对捐献者和捐献者对照进行纵向长期评估——目的是评估捐献者肝切除术和活体捐献对捐献者后续健康、生活质量和心理社会功能的影响。我们建议继续对慢性丙型肝炎患者进行移植前抗病毒治疗的LADR-A2ALL方案，以防止同种异体移植后丙型肝炎复发。然而，感染基因1型HCV的患者的病毒学反应不足以增强这些患者的反应并提高LADR-A2ALL的疗效，我们建议增加针对丙型肝炎的战略性靶向抗病毒治疗（STAT-C）。我们还建议继续研究右叶切除术后捐献者肝功能的恢复情况。在我们修改后的方案中，我们特别关注肝脏和脾脏的体积研究、SPECT 肝脾扫描以及双同位素标记的胆酸盐清除率和胆酸盐分流，以评估肝切除术后的生理变化。两项辅助研究将重点关注 LDLT 捐献者的长期结果和受者的胆道并发症。内科医生、外科医生、患者和家属的一个主要关注点是捐献者健康、功能、心理调整或社会地位的任何方面是否受到 LDLT 的影响。我们的研究将结合临床就诊和评估以及电话访谈来确定肝切除术后 2 年内的捐献者状态。最近的出版物和我们自己的分析表明，胆道并发症在 LDLT 接受者中更常见且更严重。在我们的胆道并发症的辅助研究中，我们将比较和对比 LDLT 和 DDLT 接受者之间的胆道并发症和结果。 公共卫生相关性：科罗拉多移植中心旨在确定 LDLT 中的一些关键问题——与 DDLT 相比，LDLT 的长期结果、移植前抗病毒治疗的有效性和安全性、移植后供体肝质量和肝功能的变化。肺叶切除术、供体和匹配的潜在供体对照的长期随访，以及 LDLT 后胆道并发症的发生率和严重程度。方法包括 CT 或 MRI 测量肝脏体积。 SPECT 肝脾扫描、稳定同位素和 LC/MS。