Higher Risk of Posttransplant Liver Graft Failure in Male Recipients of Female Donor Grafts Might Not Be Due to Anastomotic Size Disparity

Abstract

Background: Posttransplant liver graft failure occurs most often in male recipients of livers from female donors. The respective role of donor sex itself and the size disparity in graft vessels/bile ducts according to donor sex are unclear. Thus, we aimed to evaluate the importance of donor sex with adjustment for anastomotic size disparity between female and male donor grafts.

Methods: A total of 309 male patients without hepatic tumors who underwent living donor liver transplantation were analyzed (109 female donors and 200 male donors). The primary outcome was posttransplant graft failure (ie, retransplantation or death). Survival analysis was performed using the Cox model. Analyzed anastomosis-related factors comprised graft weight, number and size of hepatic vessels/bile ducts, and anastomosis techniques.

Results: Graft failure probabilities at 1, 6, 12, 24, and 60 months posttransplantation were 9.1%, 19.5%, 20.2%, 23.0%, and 27.0%, respectively, with female donors and 2.0%, 5.5%, 8.1%, 10.1%, and 13.5% with male donors (hazards ratio [HR], 2.29; 95% confidence interval [CI], 1.35-3.88; P = 0.002). Multivariable analysis confirmed the significance of donor sex (HR, 2.30; 95% CI, 1.14-4.67; P = 0.021) after adjustment for anastomosis-related factors. All analyzed anastomosis-related factors showed no significant association with graft failure, although size of the graft hepatic artery showed marginal significance (HR, 0.50; 95% CI, 0.25-1.01; P = 0.053). The significance of donor sex was lost when donor was older than 36 to 40 years (age of poor ovarian reserve and the end of female fertility). Our institutional pediatric recipient cohort validated the inferiority of female-to-male donation.

Conclusions: Donor sex appears to be an independent factor modulating graft failure risk in male liver transplant recipients.

FIGURE 1.

A, The probability of graft survival according to donor sex (P = 0.002) and (B) the ratio of graft failure probability with female donors to graft failure probability with male donors. Note that most differences in graft failure risk between the 2 groups were observed within the first 6 months.

FIGURE 2.

The incidence of vascular complications at 6 months posttransplantation according to donor sex. There was a significantly higher incidence of complications when grafts were from female donors versus male donors (P = 0.005).

FIGURE 3.

Graft survival according to donor sex: (A) when donor age was ≤40 years (B) when donor age was >40 years (C) interaction effect of donor sex with donor age regarding the impact on graft survival according to donor age (D) when donor age was ≤36 years and (E) when donor age was >36 years. Note that grafts from female donors were significantly associated with lower graft survival compared to male donor grafts if the donor was under 40 years (or 36 years) of age; in contrast, this age-related effect was lost in donors over 40 years (or 36 years) of age.

FIGURE 4.

Graft survival according to donor sex in pediatric male recipients: (A) the probability of graft survival (P = 0.036) and (B) the ratio of graft failure probability with female donors to graft failure probability with male donors. Female donor graft survival was significant lower than male donor graft survival in children.