Han Sangbin, Agopian Vatche A, Steggerda Justin A, Kim Irene K, Sanford Alison, Lee Yi-Te, Kwon Ji-Hye, Rhu Jin Soo, Kim Gaab Soo, Yang Ju-Dong
Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
Department of Surgery, David Geffen School of Medicine UCLA, Los Angeles, CA 90095, USA.
J Pers Med. 2025 Aug 5;15(8):357. doi: 10.3390/jpm15080357.
Sex disparity has been highlighted in personalized medicine for various human diseases including acute/chronic liver diseases. In the transplant community, greater graft failure risk in female-to-male liver transplantation (LT) has been repeatedly reported, and a recent study in living donor LT reported that the inferiority of female-to-male LT is shown only when donor age is ≤40 y. We aimed to analyze the United Network for Organ Sharing (UNOS) database to test if the poorer outcome of female-to-male LT changes by donor age of 40 y in deceased donor LT, as shown in living donor LT. In this retrospective cohort study, 11,752 adult patients in the UNOS registry who underwent deceased donor LT between 2000-2023 were analyzed. Multivariable analysis was performed to adjust the effects from transplant years, graft ischemia time, disease severity, and others. The primary outcome was graft failure. Within the subgroup of recipients with ≤40 y donors, graft failure risk was significantly greater in female-to-male LT than others (vs. female-to-female, HR = 1.43 [1.16-1.76], < 0.001; vs. male-to-female, HR = 1.46 [1.18-1.81], < 0.001; vs. male-to-male, HR = 1.26 [1.16-1.49], = 0.009). In contrast, within the subgroup of recipients with >40 y donors, the risk was comparable between female-to-male LT and other donor-recipient sex groups (vs. female-to-female, = 0.907; vs. male-to-female, = 0.781; vs. male-to-male, = 0.937). We tested various cutoff donor ages and determined that 40 y is the best cutoff value to define the risk subgroup in female-to-male LT. In the current study, we found that the sex disparity shown in living donor LT is also observed in deceased donor LT. That is, post-transplant graft failure risk was greater in female-to-male LT than other donor-recipient sex groups only when donor age was ≤40 y. In contrast, graft failure risk was comparable irrespective of donor-recipient sex combinations when donor age was >40 y.
性别差异在包括急/慢性肝病在内的各种人类疾病的个性化医疗中已得到凸显。在移植领域，女性供肝至男性受者的肝移植（LT）中移植物失败风险更高这一情况已被多次报道，并且最近一项关于活体供肝LT的研究报告称，只有当供者年龄≤40岁时，女性供肝至男性受者的LT劣势才会显现。我们旨在分析器官共享联合网络（UNOS）数据库，以检验在 deceased donor LT中，女性供肝至男性受者的LT较差结局是否会因供者年龄40岁而改变，如同在活体供肝LT中所显示的那样。在这项回顾性队列研究中，对2000年至2023年间在UNOS登记处接受 deceased donor LT的11752例成年患者进行了分析。进行多变量分析以调整来自移植年份、移植物缺血时间、疾病严重程度等因素的影响。主要结局是移植物失败。在供者年龄≤40岁的受者亚组中，女性供肝至男性受者的LT移植物失败风险显著高于其他组（与女性供肝至女性受者相比，HR = 1.43 [1.16 - 1.76]，< 0.001；与男性供肝至女性受者相比，HR = 1.46 [1.18 - 1.81]，< 0.001；与男性供肝至男性受者相比，HR = 1.26 [1.16 - 1.49]，= 0.009）。相比之下，在供者年龄>40岁的受者亚组中，女性供肝至男性受者的LT与其他供者 - 受者性别组之间的风险相当（与女性供肝至女性受者相比，= 0.907；与男性供肝至女性受者相比，= 0.781；与男性供肝至男性受者相比，= 0.937）。我们测试了各种供者年龄临界值，并确定40岁是定义女性供肝至男性受者LT风险亚组的最佳临界值。在当前研究中，我们发现活体供肝LT中显示的性别差异在 deceased donor LT中也存在。也就是说，只有当供者年龄≤40岁时，女性供肝至男性受者的LT术后移植物失败风险才高于其他供者 - 受者性别组。相比之下，当供者年龄>40岁时，无论供者 - 受者性别组合如何，移植物失败风险相当。
