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

描述（由申请人提供）：我们的项目解决了成人间活体肝移植（LDLT）的关键问题。主试验是正在进行的A2 ALL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、招募和招募患者参加试验。在主试验中，我们将比较LDLT受者的结局与同期研究的接受死亡供体肝移植（DDLT）的患者的结局。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献对供体后续健康、生活质量和心理社会功能的影响。我们建议继续LADR-A2 ALL方案，用于慢性丙型肝炎患者的移植前抗病毒治疗，以防止移植后同种异体移植物中丙型肝炎的复发。然而，感染基因型1 HCV的患者的病毒学应答不足以增强这些患者的应答并增加LADR-A2 ALL的疗效，我们建议增加针对丙型肝炎（STAT-C）的战略靶向抗病毒治疗。我们还建议继续研究右叶切除术后供体的肝功能恢复情况。在我们的修改方案中，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。两项辅助研究将关注供体的长期结局和LDLT受体的胆道并发症。医生、外科医生、患者和家属的一个关键问题是，LDLT是否会影响供体的健康、功能、心理适应或社会地位。我们的研究将结合门诊访视和评估以及电话访谈来确定肝切除术后2年内的供体状态。最近的出版物和我们自己的分析表明，胆道并发症是更常见和更严重的LDLT收件人。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受体之间的胆道并发症和结局。 公共卫生相关性：科罗拉多移植中心旨在确定LDLT的一些关键问题-LDLT的长期结局，与DDLT相比，移植前抗病毒治疗的有效性和安全性，右叶切除术后供体肝质量和肝功能的变化，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。方法将包括肝脏体积的CT或MRI测量。SPECT肝-脾扫描，稳定同位素，和LC/MS。

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.