Lee Jae Geun, Lee Juhan, Lee Jung Jun, Song Seung Hwan, Ju Man Ki, Choi Gi Hong, Kim Myoung Soo, Choi Jin Sub, Kim Soon Il, Joo Dong Jin
Department of Surgery The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul Department of Surgery, CHA Bundang Medical Center, CHA University, Bundang, Korea.
Medicine (Baltimore). 2016 Jun;95(23):e3711. doi: 10.1097/MD.0000000000003711.
Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child-Turcotte-Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients' median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver transplant recipients. However, the occurrence of HCV reactivation and CMV infection in LT patients should be monitored after rATG treatment in these patients.
肝移植(LT)后的急性细胞排斥反应可用类固醇冲击疗法治疗,但对于类固醇抵抗性急性排斥反应(SRAR)尚无理想的治疗方法。我们旨在确定应用兔抗胸腺细胞球蛋白(rATG)治疗肝移植受者SRAR的可行性及潜在并发症。我们回顾性分析了2010年1月至2015年3月在Severance医院接受LT的429例受者的病历。我们比较了类固醇敏感性急性排斥反应(SSAR;n = 23)和SRAR(n = 11)患者的临床特征及移植物存活率。我们还分析了SRAR患者接受2.5mg/kg rATG治疗6至10天后的并发症及实验室检查结果变化。SSAR和SRAR患者在性别、年龄、终末期肝病模型评分、Child-Turcotte-Pugh评分或原发病方面无显著差异,尽管死亡供体与SRAR组的关联更为频繁(P = 0.004)。所有SRAR患者对rATG治疗反应良好;治疗后,患者的中位AST水平从138降至63IU/L,中位ALT水平在rATG治疗1天后从327降至70IU/L(分别为P = 0.022和0.017)。治疗1个月后,中位天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和总胆红素水平显著下降(分别为P = 0.038、0.004和0.041)。SRAR患者LT后的中位生存期为23个月,rATG治疗后的中位生存期为22个月。不良反应包括丙型肝炎病毒(HCV)再激活、真菌血症和巨细胞病毒(CMV)感染。9例SRAR患者肝功能正常存活,1例在随访期间死于交通事故,1例死于移植物抗宿主病和真菌血症。对于肝移植受者的SRAR,给予rATG是一种有效的治疗选择,并发症可接受。然而,在这些患者接受rATG治疗后,应监测LT患者中HCV再激活和CMV感染的发生情况。