Impact of Donor Age on Graft Failure After Deceased Donor Liver Transplantation by Donor-Recipient Sex Combinations: An Analysis of the UNOS OPTN Database

<b>Background</b> 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. <b>Methods</b> 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. <b>Results</b> 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], <i>p</i> < 0.001; vs. male-to-female, HR = 1.46 [1.18-1.81], <i>p</i> < 0.001; vs. male-to-male, HR = 1.26 [1.16-1.49], <i>p</i> = 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, <i>p</i> = 0.907; vs. male-to-female, <i>p</i> = 0.781; vs. male-to-male, <i>p</i> = 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. <b>Conclusions</b> 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.