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

描述（由申请人提供）：我们的项目研究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-我们的项目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、积累和招募患者参加试验。在主试验中，我们将比较LDLT受体与同期接受已故供肝移植（DDLT）患者的结果。此外，在本试验中，我们将对供体和供体对照进行纵向长期评估，目的是评估供体肝切除术和活体捐赠对供体随后的健康、生活质量和心理社会功能的影响。我们建议将LADR-A2ALL方案继续用于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丙型肝炎复发。然而，基因型HCV感染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。我们建议增加针对丙型肝炎（STAT-C）的战略性靶向抗病毒治疗。我们也建议继续研究右肺叶切除术后供者肝功能的恢复。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，双同位素标记的胆酸清除和胆酸分流来评估肝切除术后的生理变化。两项辅助研究将重点关注供体的长期预后和LDLT受体的胆道并发症。医生、外科医生、患者和家属关心的一个关键问题是，供体健康、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访问和评估以及电话访谈来确定肝切除术后2年内供体的状态。最近的出版物和我们自己的分析表明，在LDLT受体中胆道并发症更为常见和严重。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和结局。

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.