A total of 28,222 adult patients underwent primary, single-organ liver transplantation in the United States during the study period – 9,226 (33%) were female and 18,996 (67%) were male. Baseline characteristics of the recipients are shown in . There was no significant difference in median age between female and male recipients, but females were smaller as measured by height, weight, and body mass index. A greater proportion of females were of African-American race, had NAFLD or autoimmune disease as their etiology of liver failure, and underwent living donor liver transplantation. Fewer women were transplanted for HCV-related liver disease, alcohol-related liver disease, and hepatocellular carcinoma. MELD score at transplant was significantly higher in females than in males, and this was largely driven by a higher median total bilirubin level in females compared to males, in spite of a lower median serum creatinine level. Cold ischemia time was not significantly different between the two groups.
Characteristics of Liver Transplant RECIPIENTS from March 1, 2002 through December 31, 2007
Among donors, 11,508 (41%) were female and 16,714 (59%) were male. Compared to male donors, female donors were significantly older (47 vs. 39 years; p<0.001), smaller according to height (165 vs. 178 cm; p<0.001) and weight (69 vs. 81 kg; p<0.001), and more likely to die of a cerebrovascular accident (59 vs. 35%; p<0.001). The DRI was significantly higher for female compared with male donors (1.6 vs. 1.3; p<0.001). Differences in the proportions of female grafts from donation after cardiac death, non-local origin (regional or national), split livers, or from donors with diabetes or hypertension were statistically significant, but of unlikely clinical significance (). There were no significant differences in the proportion of female donors by region or by year of transplant (data not shown).
Characteristics of Liver DONORS from March 1, 2002 through December 31, 2007
Male recipients were less likely than female recipients to receive a gender-mismatched graft (37% vs. 50%; p<0.001). One, 3- and 5-year survival rates for recipients of a gender mismatched graft (regardless of recipient gender) were 83%, 72%, and 65%, respectively, versus 86%, 75%, and 68% for a gender matched graft (p<0.001). Compared to recipients of a gender matched graft, recipients of a gender mismatched graft were at 11% higher risk of graft loss [hazard ratio (HR), 1.11; 95% confidence interval (CI), 1.06-1.16; p<0.001].
The Kaplan-Meier survival curves for each donor-recipient gender pairing are shown in the . Graft survival rates at 1-, 3-, and 5- years were 86%, 75%, 67% for M→M matched recipients, 85%, 75%, 68% for F→F matched recipients, 83%, 71%, 64% for F→M mismatched recipients, and 84%, 74%, and 68% for M→F mismatched recipients (p<0.001). In univariable analysis, F→M mismatched recipients, compared to M→M matched recipients, were at increased risk of graft loss (HR, 1.17; 95%CI, 1.11-1.23; p<0.001), whereas M→F recipients were not [HR, 1.02; 95%CI, 0.96-1.09; p=0.46; ]. After adjustment for clinically relevant recipient, donor, and transplant-related factors, there was no longer an association between F→M mismatch and graft loss (). The dominant donor characteristics affecting the association between gender mismatch and graft loss were donor age and donor height, although donation after cardiac death, stroke as the cause of death, split liver, and donor diabetes were also predictive of graft loss ().
Unadjusted Kaplan-Meier Survival Curves by Donor-Recipient Gender Pairing.
Cox analyses of the association between donor-recipient gender mismatch and graft failure
In a post hoc analysis to further evaluate the association between donor-recipient gender-pairing and graft loss, we observed an important effect modification by recipient HCV-status (). In univariable analysis, compared to M→M matched recipients, female HCV recipients experienced an increased hazard of graft failure regardless of donor gender. This was not seen among non-HCV recipients (). Adjustment for other factors associated with graft loss eliminated the association between F→F matching and graft loss among HCV recipients, but not among M→F mismatched recipients (). In contrast, among non-HCV recipients, there was no increased risk of graft loss among the M→F group ().
Comparison of univariable and multivariable analyses to evaluate the association between donor-recipient gender mismatch and graft loss, stratified by recipient HCV-status