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成人肝移植后供体特异性同种抗体的流行率、危险因素和影响。

Prevalence, Risk Factors, and Impact of Donor-Specific Alloantibodies After Adult Liver Transplantation.

机构信息

Unité de Transplantation Hépatique, Hospices Civils de Lyon, Lyon, France.

Etablissement Français du Sang, Laboratoire d'Histocompatibilité, Lyon, France.

出版信息

Liver Transpl. 2018 Aug;24(8):1091-1100. doi: 10.1002/lt.25177.

Abstract

The incidence and impact of anti-human leukocyte antigen donor-specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single-center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center. The study population mainly consisted of male patients, the mean age was 52.4 years, and the main indication was alcoholic cirrhosis (54.1%). From the 297 patients included in the cross-sectional study, 14 (4.7%) had preformed DSAs, and 59 (19.9%) presented de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years). Multivariate analysis found that female donor sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.12-2.01; P = 0.01) and delay between LT and DSA screening (HR, 1.10; 95% CI, 1.01-1.20; P = 0.03) were associated with occurrence of de novo DSAs. From the 190 patients included in the subgroup longitudinal analysis, exposure to tacrolimus (mean trough level during the periods 0-2 years and 0-3 years) was significantly lower for patients having DSAs at 5 years. Concerning histology, only acute rejection (P = 0.04) and portal fibrosis ≥2 (P = 0.02) were more frequent at 1 year for patients with DSAs. Patient survival and graft survival were not significantly different according to the presence or not of DSAs at 1 year. Among the 44 patients who had de novo or persistent preformed DSAs, the diagnosis of antibody-mediated rejection was made in 4 (9.1%) patients after 1, 47, 61, and 74 months following LT. In conclusion, the results of the present study suggest that DSAs are observed in a minority of LT adult patients, with limited overall impact on graft and patient outcome.

摘要

肝移植(LT)后抗人类白细胞抗原供体特异性抗体(DSA)的发生率和影响仍存在争议,且尚未得到广泛研究。本研究旨在评估 DSA 的发生率,确定 DSA 发展的危险因素,并了解大量成年 LT 受者中 DSA 的影响。这项单中心回顾性研究纳入了 2000 年至 2010 年期间在我院接受首次 LT 的所有成年患者。研究人群主要为男性患者,平均年龄为 52.4 岁,主要适应证为酒精性肝硬化(54.1%)。在纳入的 297 例横断面研究患者中,14 例(4.7%)存在预先形成的 DSA,59 例(19.9%)出现新形成的 DSA(1 年时为 12.2%,5 年时为 13.4%,10 年时为 19.5%)。多变量分析发现,女性供体性别(风险比[HR],1.50;95%置信区间[CI],1.12-2.01;P=0.01)和 LT 与 DSA 筛查之间的时间延迟(HR,1.10;95%CI,1.01-1.20;P=0.03)与新形成的 DSA 相关。在纳入的亚组纵向分析的 190 例患者中,在第 0-2 年和第 0-3 年期间,DSA 患者的他克莫司(平均谷浓度)暴露量明显更低。在组织学方面,只有急性排斥反应(P=0.04)和门静脉纤维化≥2(P=0.02)在 1 年时在 DSA 患者中更为常见。根据 1 年时是否存在 DSA,患者的生存率和移植物生存率没有显著差异。在 44 例出现新形成或持续存在预先形成的 DSA 的患者中,在 LT 后 1、47、61 和 74 个月,有 4 例(9.1%)患者被诊断为抗体介导的排斥反应。总之,本研究结果表明,DSA 见于少数 LT 成年患者,对移植物和患者预后的总体影响有限。

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