In this study, the association of recipient/donor race matching and mortality was examined for HCV-related liver transplantation. Several important findings were observed. First, while black recipients appear to have higher mortality after liver transplantation for HCV, this is largely limited to black recipients who receive a liver from a white donor. The lowest cumulative survival rates were consistently observed in this group of patients, with 1, 2 and 5 year survival rates of 86%, 74%, and 56%. By contrast, black recipients of livers from black donors had 1, 2 and 5 year survival rates of 90%, 82% and 70%, rates which are not significantly different from white recipients with white donors (91%, 85% and 72%, respectively). While it appears that black recipients of livers from Hispanic donors may also have decreased survival rates after transplantation for HCV, this finding needs to be confirmed in larger studies given the small number in this group.
The second important observation is that the interaction between donor and recipient race and its impact on patient survival is not limited to black recipients. White recipients with Hispanic donors had a 19% increase in mortality compared to white recipients with white donors, even after adjustment for other differences in multivariable analysis. However, receipt of a liver from a black donor did not impact the outcome of white recipients. Finally, for Hispanic recipients, the best outcomes occurred in the subset of patients who received livers from black donors. Thus, all races studied were impacted in some way by recipient/donor race mismatching of organs.
The third observation is that, overall, Hispanics had a lower risk of death compared to white and black recipients. This was most pronounced in the subset of patients who received a liver from a black donor, with an adjusted HR of 0.64 (p=0.005) compared to the white recipient/white donor group.
These results extend the knowledge gained from prior studies. Several earlier studies have shown black recipients to have lower survival after liver transplantation (4
), especially when transplanted for HCV (4
). This was observed in our study as well. However, in this study, we found that the lower survival among blacks was limited to those who received a liver from a white recipient. Similar results have been observed by Pang et al. who demonstrated that HCV-infected blacks transplanted with livers from white donors had lower graft survival (20
). Interestingly, in their study, this result did not occur in patients transplanted for indications other than HCV. In addition, the white recipient/black donor combination led to worse outcomes, compared to whites with white donors (20
). This result was not seen in our study, a finding that may be attributed to the different outcomes measured (patient survival in our study vs graft survival in the study by Pang et al.), or differences in study populations. The findings from these two studies emphasize the need to consider both donor and recipient race when assessing mortality rates in those transplanted for HCV.
Past studies examining the impact of donor race have provided mixed results. Feng et al., in creating a donor risk index, found black donor race to be associated with worse outcomes (22
). In a more recent study by Asrani et al., they did not find an association between black recipient race and liver graft failure after controlling for numerous variables, including transplant center (21
). However, when analyses were stratified by recipient race, they did observe that black recipients of organs from white donors had an increased risk of graft failure. Comparing the results from these two studies to the present one is difficult for several reasons. First, the studies by Feng and Asrani included patients who had undergone liver transplantation for all indications (21
). Prior studies have shown that the impact of recipient and donor race appears to be enhanced for HCV-related transplantation (4
). Further, the study by Feng et al. did not appear to account for the interaction between donor and recipient race (20
). While the study by Asrani et al. did assess for such an interaction, they did not include Hispanics, and they addressed the interaction by stratifying by recipient race (21
). This allowed a comparison between groups of the same recipient race but HRs comparing to other race groups could not be calculated.
There are well-documented differences between race groups in the natural history of HCV, such as a lower rate of spontaneous clearance of virus and a slower progression of HCV-related liver disease in blacks in the non-transplant setting (24
). Combined with the well-known differences in HCV treatment response rates between race groups (27
), it is reasonable to hypothesize that differences in mortality may be secondary to differences in HCV pathogenesis post-transplantation. In this study, we did find that among blacks, those with black donors had the lowest reported rates of HCV recurrence. Pang et al. also found a higher rate of graft failure due to HCV recurrence for black recipients, but did not stratify by donor race (20
). Comparing graft failure etiologies based on UNOS data is problematic, however, as these data are often missing, standard criteria for determining the cause of graft failure are lacking, and biopsy confirmation of a diagnosis is not required. Further investigations on the differences in HCV recurrence according to recipient/donor race matching after liver transplantation are necessary to address this question.
While this study provides important findings, it is imperative to highlight its limitations. The UNOS database is a rich resource as it captures all transplants performed in the United States. However, as with any large database, it is limited in the information that it collects. As with many retrospective studies, detailed information regarding immunosuppression, treatment of HCV recurrence and rejection, and compliance to medical treatments is lacking. In addition, not all variables in the database are collected for all patients, and racial data are self-reported. Finally, there is no accompanying tissue repository to confirm outcomes or allow additional investigations. However, findings on survival from large retrospective databases often are the first to identify important observational findings that then can be confirmed with further investigation.
It might appear reasonable on the basis of the present study to recommend a change in donor matching policy to put liver allograft's from black donors into black recipients. However, we believe that a more comprehensive discussion is needed about access to and outcome after liver transplantation in African Americans in the US. A policy change to link black donors with black recipients could have the unintended consequence of restricting black patients access to liver transplantation, at a time when black patients are disadvantaged already in access to this therapy. Moreover, a broader global discussion is needed about donor-recipient matching, since it is clear, from this and other studies that the prognosis of the donor organ and recipient can be assessed with apriori knowledge of the donor and recipient race as well as other variables. However, instituting a policy to maximize the outcome after transplantation (`utility of transplantation') rather than giving priority to the sickest patient on the waiting list (`urgency') would be a radical change from present practices, and in conflict with the law governing transplantation, also known as `the final rule'.
In conclusion, this study highlights that for HCV-related liver transplantation, the effect of recipient race varies according to the race of the donor, especially for black recipients. Future studies that assess mortality risk need to account for this interaction. Additionally, the mechanisms for the present observations need to be understood, both for their equity implications for patients of different races, as well because it may reveal important information about graft acceptance and success. Unfortunately, the donor pool for liver transplantations is limited, even more so if attempts are made to match donor and recipient races, particularly with respect to black recipients. There must be enhanced public awareness of the need for organ donation.