Tamura Kei, Tohyama Taiji, Watanabe Jota, Nakamura Taro, Ueno Yoshitomo, Inoue Hitoshi, Honjo Masahiko, Sakamoto Katsunori, Takai Akihiro, Ogawa Kohei, Takada Yasutsugu
Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Japan.
Hepatol Res. 2019 Aug;49(8):929-941. doi: 10.1111/hepr.13352. Epub 2019 May 8.
The impact of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) on living donor liver transplantation (LDLT) is unclear. The aim of this study was to investigate the association between DSAs and short-term outcomes in LDLT recipients, and to clarify the clinical impact of DSAs.
Anti-HLA antibodies were screened in preoperative serum samples taken from 40 liver transplant recipients at Ehime University (Toon, Japan) between August 2001 and July 2015. Screening was carried out using the Flow-PRA method, and DSAs were detected in anti-HLA antibody-positive recipients using the Luminex single-antigen identification test. A mean fluorescence intensity of 1000 was used as the cut-off for positivity. We retrospectively reviewed the clinical courses of patients who were DSA-positive to elucidate early clinical manifestations in LDLT recipients.
Fifteen (12 female and 3 male) patients (38%) had anti-HLA antibodies. Eight of the 15 anti-HLA antibody-positive patients were positive for DSAs, and all were women. The 90-day survival rate of DSA-positive patients (50%) was significantly lower than that of DSA-negative patients (84.4%) (0.0112; Wilcoxon test). On univariate analysis, the DSA-positive rate was significantly higher in the 90-day mortality group. Postoperatively, the incidence of acute cellular rejection was higher in DSA-positive than DSA-negative patients. Thrombotic microangiopathy developed only in DSA-positive patients. We found no relationship between DSA status and bile duct stricture.
Preformed DSAs could be associated with elevated 90-day mortality in LDLT recipients. Further large-scale studies are required to verify the risk associated with DSAs in LDLT.
供者特异性抗人白细胞抗原(HLA)抗体(DSA)对活体供肝肝移植(LDLT)的影响尚不清楚。本研究旨在探讨DSA与LDLT受者短期预后之间的关联,并阐明DSA的临床影响。
对2001年8月至2015年7月期间在日本爱媛大学(东温市)接受肝移植的40例受者术前血清样本进行抗HLA抗体筛查。采用流式细胞仪检测群体反应性抗体(Flow-PRA)方法进行筛查,使用Luminex单抗原鉴定试验在抗HLA抗体阳性受者中检测DSA。以平均荧光强度1000作为阳性判断标准。我们回顾性分析了DSA阳性患者的临床病程,以阐明LDLT受者的早期临床表现。
15例(12例女性,3例男性)患者(38%)存在抗HLA抗体。15例抗HLA抗体阳性患者中有8例DSA阳性,均为女性。DSA阳性患者的90天生存率(50%)显著低于DSA阴性患者(84.4%)(P = 0.0112;Wilcoxon检验)。单因素分析显示,90天死亡组的DSA阳性率显著更高。术后,DSA阳性患者的急性细胞排斥反应发生率高于DSA阴性患者。血栓性微血管病仅发生在DSA阳性患者中。我们发现DSA状态与胆管狭窄之间无相关性。
预先存在的DSA可能与LDLT受者90天死亡率升高有关。需要进一步开展大规模研究以验证LDLT中与DSA相关的风险。