Waiting List and Kidney Transplant Outcomes for Patients with Hepatitis C Infection

项目摘要 丙型肝炎（HCV）病毒感染在美国慢性透析患者中很常见 并与死亡和发病风险升高相关。不同透析单位的感染率差异很大， 估计在2 - 14%之间。HCV感染使透析患者的死亡率增加1.6 - 2.4 折与透析相比，肾移植在生存率和生活质量方面提供了实质性的改善， 即使是在高风险亚组，如老年人和糖尿病患者中。不幸的是，美国的移植手术 登记处没有记录等待登记的患者中的HCV血清状态。肾移植结果的研究 因此，HCV+患者受到单中心人群、短期随访、仅关注 移植后的结果，以及对更广泛的HCV+人群的普遍性的担忧。不清楚是否 对于HCV+患者，肾移植比透析有生存益处，如果接受HCV+供体， 肾影响这一益处。丙型肝炎病毒在透析和肾移植中的前景已经大大改变， 通过批准直接作用的抗病毒药物（DAA）改变;然而，基于DAA的HCV的理想时机 治疗及其对移植结果的影响尚未确定。 HCV+肾移植候选人的最佳移植策略仍然未知。相比 未感染的肾移植候选人，HCV+候选人有额外的风险因素， 等待名单，包括肝病进展，以及更高的合并症负担，包括 糖尿病和心血管疾病（CVD），这可能会影响肾移植的获得和死亡率。 移植可以降低心血管疾病的风险，但可能会恶化其他健康状况，如血糖控制。还有， HCV+候选人有接受HCV+捐赠者肾脏的独特选择，这种做法存在风险 病毒性并发症如肝损伤。接受HCV+器官与等待HCV-的好处 阴性肾，可能只有健康状况恶化或预期等待时间较长的个人才能实现。 虽然移植前使用DAA治疗可能会降低因医学合并症而被除名的风险， 可能会无意中增加等待时间和死亡的风险，由于无法使用HCV+供体。 使用由国家透析提供者收集的信息以及移植的独特数据集 结果和医疗保险索赔，我们将确定肾移植是否与生存相关 与慢性透析相比，在等待上市的HCV+患者的不同国家样本中获益。我们将 检查接受HCV+肾脏是否比等待肾移植更有益， HCV阴性献血者最后，我们将比较等待名单上的HCV+患者的移植时间， 用DAA治疗与未治疗的比较。鉴于我们持续访问透析提供者数据和最大的队列， 美国HCV+肾移植候选人的聚集，研究结果将激励未来的研究建议 以及旨在优化终末期肾病HCV+患者护理的额外数据链接。

PROJECT SUMMARY Hepatitis C (HCV) viral infection is common among chronic dialysis patients in the United States (US) and associated with elevated risks of death and morbidity. Infection rates vary widely across dialysis units, with estimates ranging from 2 – 14%. HCV infection increases the death rate among dialysis patients by 1.6 – 2.4 fold. Kidney transplantation offers substantial improvements in survival and quality of life compared to dialysis, even in high risk subgroups such as the elderly and patients with diabetes. Unfortunately, the US transplant registry does not record HCV serostatus among wait-listed patients. Studies of kidney transplant outcomes for HCV+ patients have therefore been limited by single center populations, short follow-up, exclusive focus on post-transplant outcomes, and concerns about generalizability to the wider HCV+ population. It is unknown if there is a survival benefit of kidney transplant over dialysis for HCV+ patients, and if receipt of an HCV+ donor kidney affects this benefit. The landscape of HCV in dialysis and kidney transplantation has been greatly altered by the approval of direct acting antiviral agents (DAAs); however the ideal timing of DAA-based HCV therapy and its effects on transplant outcomes have not been determined. The optimal transplant strategy for HCV+ kidney transplant candidates remains unknown. Compared to uninfected kidney transplant candidates, HCV+ candidates have additional risk factors for removal from the waiting list, including progression of their liver disease, and a higher burden of comorbidities, including diabetes and cardiovascular disease (CVD), which can affect access to kidney transplant and mortality. Transplantation may reduce CVD risk, but may worsen other health conditions such as glycemic control. Also, HCV+ candidates have the unique option of accepting kidneys from HCV+ donors, a practice that carries risks of viral complications such as liver injury. The benefits of accepting a HCV+ organ, versus waiting for a HCV- negative kidney, may only be realized by individuals with deteriorating health or anticipated long waiting times. While treatment with DAAs pre-transplant may decrease the risk of delisting due to medical comorbidities, it may inadvertently increase waiting times and risk of death due to inability to use HCV+ donors. Using a unique dataset with information collected by a national dialysis provider as well as transplant outcomes and Medicare claims, we will determine whether kidney transplant is associated with a survival benefit compared to chronic dialysis in a diverse, national sample of wait-listed HCV+ patients. We will examine whether acceptance of HCV+ kidneys offers benefit versus waiting for a kidney transplant from an HCV-negative donor. Finally, we will compare time to transplant among wait-listed HCV+ patients who are treated versus untreated with DAAs. Given our ongoing access to dialysis provider data and the largest cohort of US HCV+ kidney transplant candidates ever assembled, the findings will motivate future research proposals and additional data linkages aimed at optimizing the care of HCV+ patients with end-stage renal disease.