Johnson John C, Engebretsen Trine, Mujtaba Muhammad, Stevenson Heather L, Kulkarni Rupak, Scott Lea A, Moghe Akshata, Gamilla-Crudo Ann Kathleen, Hussain Syed, Kueht Michael
Department of Surgery, Division of Multiorgan Transplant and Hepatobiliary Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0655, USA.
Department of Medicine, Division of Transplant Nephrology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0655, USA.
Surg Pract Sci. 2024 Feb 6;16:100236. doi: 10.1016/j.sipas.2024.100236. eCollection 2024 Mar.
In renal transplantation, donor hepatitis C virus (HCV) status is crucial to consider when selecting a recipient given the high likelihood of transmission. We analyzed the effect of donor HCV status on post-renal transplant rejection and virologic infectious outcomes using electronic health record data from multiple US health care organizations.
Using real world data from electronic health records of renal transplant recipients, a propensity score-matched case-control study of one-year renal transplant outcomes was conducted on cohorts of HCV-negative recipients who received an organ from an HCV-positive donor (HCV D+/R-) versus from an HCV-negative donor (HCV D-/R-). Donor HCV positivity was defined as new recipient HCV positivity within 30 days post-transplant. Cohorts were matched by major risk factors for rejection including age, gender, race, etiologies of end-stage renal disease, dialysis dependence, donor type, induction immunosuppression, and virologic lab studies. The primary outcome was one-year incidence of rejection. Secondary outcomes included longitudinal measures of liver and kidney function, incidence of non-HCV viremia, and DAA treatment pathways and responses.
Data from 900 renal transplant recipients were analyzed, 450 subjects per group (D+/R-, D-/R-). Mean age at transplant was 57.1 ± 11.9 years, 60 % were male, and 38 % were African American. Kaplan-Meier analysis showed a significantly increased incidence of one-year rejection for HCV D-/R- compared to HCV D+/R- (16.6% vs 22.8 %, = 0.02). This difference did not persist on a sub-analysis excluding subjects with delayed graft function (DGF) (16.3% vs 19.2 %, = 0.25). Although mean eGFR was initially higher in HCV D+/R-, there were no significant differences in liver or kidney allograft function at 12 months. There was no significant difference for composite viremia (CMV/EBV/BK; 37.66% vs 31.60 %, = 0.07). The most common DAA regimen was glecaprevir/pibrentasvir (52.8 %). DAA treatment responses were excellent, with most subjects having a negative viral load by 90 days (mean: 1.7 ± 1.9 log units/mL).
Donor HCV positivity did not negatively impact one-year rejection outcomes post-renal transplantation. Importantly, this effect was not biased by age. Anti-HCV treatment was effective and liver and kidney function were excellent at one-year post-transplant. These data support the continued expansion of the donor pool by utilizing organs from HCV-positive donors in the era of anti-HCV direct-acting antiviral therapies.
在肾移植中,鉴于丙型肝炎病毒(HCV)传播的可能性很高,供体HCV状态是选择受体时需要考虑的关键因素。我们使用来自多个美国医疗保健机构的电子健康记录数据,分析了供体HCV状态对肾移植后排斥反应和病毒学感染结果的影响。
利用肾移植受者电子健康记录中的真实世界数据,对接受来自HCV阳性供体(HCV D+/R-)与HCV阴性供体(HCV D-/R-)器官的HCV阴性受体队列进行了倾向评分匹配的病例对照研究,以评估一年的肾移植结果。供体HCV阳性定义为移植后30天内新受体HCV阳性。队列根据排斥反应的主要危险因素进行匹配,包括年龄、性别、种族、终末期肾病病因、透析依赖、供体类型、诱导免疫抑制和病毒学实验室检查。主要结局是一年的排斥反应发生率。次要结局包括肝脏和肾脏功能的纵向指标、非HCV病毒血症的发生率以及直接抗病毒药物(DAA)治疗途径和反应。
分析了900名肾移植受者的数据,每组450名受试者(D+/R-,D-/R-)。移植时的平均年龄为57.1±11.9岁,60%为男性,38%为非裔美国人。Kaplan-Meier分析显示,与HCV D+/R-相比,HCV D-/R-的一年排斥反应发生率显著增加(16.6%对22.8%,P = 0.02)。在排除移植肾功能延迟(DGF)受试者的亚分析中,这种差异没有持续存在(16.3%对19.2%,P = 0.25)。虽然HCV D+/R-的平均估算肾小球滤过率(eGFR)最初较高,但12个月时肝脏或肾脏移植功能没有显著差异。复合病毒血症(CMV/EBV/BK)没有显著差异(37.66%对31.60%,P = 0.07)。最常见的DAA方案是glecaprevir/pibrentasvir(52.8%)。DAA治疗反应良好,大多数受试者在90天时病毒载量为阴性(平均:1.7±1.9 log单位/mL)。
供体HCV阳性对肾移植后一年的排斥反应结果没有负面影响。重要的是,这种影响不受年龄的偏差。抗HCV治疗有效,移植后一年肝脏和肾脏功能良好。这些数据支持在抗HCV直接抗病毒治疗时代,通过利用来自HCV阳性供体的器官来持续扩大供体库。