The Effect of Donor Race on the Survival of Black Americans Undergoing Liver Transplantation for Chronic Hepatitis C

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1 LIVER TRANSPLANTATION 15: , 2009 ORIGINAL ARTICLE The Effect of Donor Race on the Survival of Black Americans Undergoing Liver Transplantation for Chronic Hepatitis C Phillip S. Pang, 1,2 * Ahmad Kamal, 2,3 * and Jeffrey S. Glenn 2,4 Divisions of 1 Infectious Diseases and Geographic Medicine and 2 Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA; 3 Division of Gastroenterology and Hepatology, Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA; and 4 Palo Alto Veterans Administration Medical Center, Palo Alto, CA The purpose of this study was to determine the effect of donor race on the outcome of black patients with chronic hepatitis C infection who undergo liver transplantation. The records for deceased donor liver transplants that occurred in the United States between January 1998 and December 2007 were obtained from the United Network for Organ Sharing. 26,212 records contained sufficient data to be included in the analysis. Of these, 11,989 (45.7%) records were for patients positive for hepatitis C virus (HCV) and 1292 (4.9%) were for patients both HCV-positive and black. Black recipients with white donors were found to have significantly worse outcomes than all other recipient-donor race combinations (P 0.001). The crude 5-year survival rate for black recipients who had a black donor was 14% higher than the 5-year survival rate for black recipients who had a white donor. Multivariate regression analysis determined that a graft from a race-unmatched donor was an independent risk factor for graft failure (hazard ratio 1.41, 95% confidence interval ) among HCV-positive black recipients but not among HCV-negative black recipients after adjustments for donor age, recipient age, cold ischemia time, serum creatinine, serum bilirubin, diabetes mellitus, body mass index, and donor cytomegalovirus status. The observation that race-unmatched grafts are a risk factor in HCV-positive black recipients, but not in HCV-negative black recipients, suggests an alteration of the graft-host relationship by HCV. In conclusion, our results suggest that HCV-positive black recipients who undergo liver transplantation can have increased graft survival if their donors are black, with survival rates approaching those of white liver transplant recipients. Liver Transpl 15: , AASLD. Received February 18, 2009; accepted May 15, See Editorial on Page 1001 Prior to the Model for End-Stage Liver Disease (MELD) era, black patients were underrepresented on the liver transplant waiting list and were more likely to die while awaiting transplantation. The current MELD scoring system appears to have eliminated racial differences in access to transplantation. 1 However, for unclear reasons, black recipients continue to experience lower posttransplant graft survival rates than their white peers. 2-4 In the United States, the leading indication for Abbreviations: BMI, body mass index; CI, confidence interval; CMV, cytomegalovirus; CVA, cerebrovascular accident or stroke; HCV, hepatitis C virus; HLA, human leukocyte antigen; HR, hazard ratio; INR, international normalized ratio; MELD, Model for End-Stage Liver Disease; NK, natural killer; UNOS, United Network for Organ Sharing. The content of this article is the responsibility of the authors alone and does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This work was supported by a Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, the National Institutes of Health (RO1 DK066793), and the Center for Translational Research in Chronic Viral Infections (to Jeffrey S. Glenn). Phillip S. Pang was supported by a Stanford Dean s Fellowship and a T32 Genomics Training Grant (AI070502). This work was also supported by the Health Resources and Services Administration (contract C). *These authors contributed equally to this study. Additional Supporting Information may be found in the online version of this article. Address reprint requests to Jeffrey S. Glenn, M.D., Ph.D., Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, CCSR 3115A, 269 Campus Drive, Palo Alto, CA Telephone: ; FAX: ; jeffrey.glenn@stanford.edu DOI /lt Published online in Wiley InterScience ( American Association for the Study of Liver Diseases.

2 DONOR RACE AND SURVIVAL OF BLACK AMERICANS 1127 liver transplantation for both blacks and whites is hepatitis C virus (HCV). 5 This infection is twice as common in the black population compared to the white population. 3 Black patients are also more likely than white patients to be infected with HCV genotype 1, the genotype that is the most refractory to current therapy. 3 Unsurprisingly, a failure to adequately clear HCV increases the risk of cirrhosis and the need for liver transplantation. Because of the higher prevalence of whites in the liver donor pool, black recipients often receive a graft from a racially unmatched donor. We hypothesized that the poor graft survival rates seen among black liver transplant recipients might be due in part to having a racially unmatched donor. In this study, we sought to test this hypothesis by determining the extent to which such mismatch accounts for the higher mortality seen among HCV-infected black patients who undergo liver transplantation. Figure 1. Kaplan-Meier survival curves: HCV-positive white liver transplant recipients versus HCV-positive black liver transplant recipients. Abbreviation: HCV, hepatitis C virus. PATIENTS AND METHODS Study Population and Definitions Records of all adult liver transplants performed in the United States between January 1998 and December 2007 were obtained from United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research files (created on May 20, 2008). These files contain 1 record per transplant event, along with data from the most recent follow-up visit for each patient. Data are collected by each transplant center and transmitted to UNOS at the time of registration, time of transplant, 6 months after transplant, and annually thereafter. This 10-year period, spanning both the pre-meld and post-meld eras, was initially chosen to ensure an adequate number of black patients with black donors. To determine whether our results were applicable to current practice standards, a separate analysis was performed that was restricted to transplants performed after February 2002, the post-meld period. The following exclusion criteria were applied: missing HCV status, a donor or recipient race other than non-hispanic white or non-hispanic black, use of a non heart-beating donor, multi-organ transplant, split liver transplant, and use of a living donor. Race was self-identified by patients when they were registered in the UNOS database (see Supporting Fig. 1 for exclusion statistics). The hepatitis C cohort was defined as those patients with documented detection of an antibody to HCV (anti- HCV) and a diagnosis of either type C cirrhosis or chronic or acute hepatitis C. The hepatitis C negative cohort consisted of patients with documented negative anti-hcv and a diagnosis other than type C cirrhosis, chronic or acute hepatitis C, type B or C cirrhosis, or alcoholic cirrhosis with hepatitis C. The post-meld cohort was defined as those patients receiving a liver transplant after February Graft failure was defined as death or the need for retransplantation. Statistical Analyses The primary outcome measure was graft survival in white transplant patients versus black transplant patients who received grafts from race-matched donors versus unmatched donors. Overall survival was computed with the Kaplan-Meier estimator. Comparisons of survival between groups were performed with the logrank test. Cox proportional hazards regression modeling was used to determine whether donor race was an independent predictor of graft survival following transplantation. To build the model, we first performed univariate analysis for all variables that either (1) had previously been shown to independently predict posttransplant outcome or (2) had a biologically plausible reason for affecting posttransplant mortality. We then included in our multivariate analysis those variables shown to be significant predictors of outcome in our univariate analysis. For the regression analyses, observations that contained a missing value for any predictor were excluded; the percentage of records included in each regression analysis is indicated in the regression table. To address the impact of missing data, a second model was constructed that excluded no records and used single imputation for any missing variables. The Breslow-Day statistic for homogeneity across strata was used to investigate effect modification. Additionally, a combined model that allowed for the possibility of 2-way and 3-way interactions among race, HCV status, and donor-recipient mismatch was constructed to quantitate possible combinatorial effects. Fisher s exact test and the chi-square statistic (for larger numbers) were used to determine if the proportion of patients with graft-host human leukocyte antigen (HLA) mismatch at the A, B, and DR loci was statistically different for patients with a black donor and patients with a white donor. P values were 2-sided and were not adjusted for multiple testing. Analyses were

3 1128 PANG, KAMAL, AND GLENN TABLE 1. Patient Characteristics for Hepatitis C-Positive Patient Cohort White White Recipient Black Black Recipient Donor Donor P Value* Donor Donor P Value P Value n Age (years) 51.3 (7.30) 51.7 (7.28) (7.33) 52.5 (6.83) Female sex (%) Donor age (years) 40.6 (16.9) 39.3 (16.0) (16.6) 39.4 (16.9) BMI (kg/m 2 ) 28.7 (5.31) 28.9 (5.60) (5.70) 23.3 (5.06) INR 1.77 (1.2) 1.81 (1.8) (1.5) 1.94 (1.1) Creatinine (mg/dl) 1.27 (0.96) 1.25 (0.95) (1.14) 1.52 (0.98) Bilirubin (mg/dl) 6.1 (9.1) 5.9 (8.8) (8.5) 6.4 (8.4) Albumin (mg/dl) 2.9 (0.82) 2.9 (0.66) (0.69) 2.7 (0.75) Cold ischemia time (hours) 7.82 (3.84) 7.48 (3.89) (3.60) 7.85 (4.01) Warm ischemia time (minutes) 43 (19.9) 43 (20.0) (20.0) 44 (21.0) Donor CMV (%) Recipient CMV (%) Diabetes (%) Black donor (%) Black White NOTE: Data are presented as mean (standard deviation). Abbreviations: BMI, body mass index; CMV, cytomegalovirus; INR, international normalized ratio. *White donors versus black donors for HCV-positive white transplant recipients. Black donors versus white donors for HCV-positive black transplant recipients. HCV-positive white transplant recipients versus HCV-positive black transplant recipients. carried out with SAS version 9.1 (SAS Institute, Cary, NC). RESULTS Of the 50,435 adult liver transplants listed in the UNOS database between January 1998 and December 2007, 26,212 met inclusion criteria. Of these, 11,989 (45.7%) were for HCV-positive patients, 2646 (10.1%) were for black recipients, and 1292 (4.9%) were for black recipients who were HCV-positive. Of these 1292 HCV-positive black transplant recipients, 316 had black donors and 976 had white donors. The characteristics of these patients are shown in Tables 1 and 2. The HCV-positive black patient cohort contained more women, was slightly older, had higher baseline creatinine levels and lower baseline albumin levels, was more likely to be cytomegalovirus (CMV)- seropositive, and was more likely to have diabetes mellitus in comparison with the HCV-positive white patient cohort. The median follow-up for all patients was 919 days. Figure 1 shows the Kaplan-Meier survival curves for HCV-positive black transplant recipients versus HCVpositive white transplant recipients. As previously observed, HCV-positive black transplant recipients have a lower graft survival rate than HCV-positive white recipients (P 0.001). 4 As the majority of transplant donors in the United States are white, the large majority (76%) of these black transplant recipients had white donors. Figure 2A compares matched and unmatched recipient-donor race in HCV-positive liver transplant patients. Black recipients with white donors had significantly worse outcomes than all other recipient-donor race combinations (P 0.001). The 5-year graft survival rate for black recipients who had white donors was 45%. In comparison, the 5-year survival rate for black recipients who had black donors was 59%, an absolute increase in survival of 14%. HCV-positive black recipients with black donors had survival rates similar to those of HCV-positive white recipients overall (59% versus 63%). Figure 2B shows the Kaplan-Meier survival curves for matched recipient-donor race versus unmatched recipient-donor race in HCV-negative transplant patients. This HCV-negative transplant population did not demonstrate a notable difference in graft survival between black recipients with black donors and those with white donors; 5-year graft survival was 63% versus 66%, respectively. This analysis also found worse overall outcomes for HCV-positive transplant patients versus HCV-negative transplant patients and was consistent with prior observations. 6 The corresponding Kaplan- Meier curves for patient survival can be found in Supporting Fig. 2, and they depict trends quite similar to those of the graft survival curves shown in Fig. 2. Multivariate Cox proportional hazards regression modeling (Table 3) determined that having a graft from a white donor was an independent risk factor for graft failure among HCV-positive black recipients [hazard ratio (HR) 1.41, P 0.005] after we controlled for factors previously found to be associated with differences in transplant outcome: donor age, recipient age, cold ischemia time, serum creatinine, serum bilirubin, diabetes mellitus, body mass index, and donor CMV status. 7-9 Of note, in univariate analyses, gender, warm

4 DONOR RACE AND SURVIVAL OF BLACK AMERICANS 1129 TABLE 2. Patient Characteristics Hepatitis C Negative White Recipient Black Recipient P Value* n 12,863 1,354 Age (years) 52.5 (11.4) 43.1 (13.0) Female sex (%) Donor age (years) 41.1 (18.1) 38.9 (17.9) BMI (kg/m 2 ) 28.2 (6.00) 27.2 (6.11) 0.11 INR 1.89 (1.4) 2.25 (2.1) Creatinine (mg/dl) 1.39 (1.08) 1.46 (1.29) 0.05 Bilirubin (mg/dl) 7.8 (10.1) 12.8 (12.8) Albumin (mg/dl) 2.9 (0.69) 2.7 (0.72) Cold ischemia time (hours) 7.72 (3.62) 7.86 (3.87) 0.23 Warm ischemia time (minutes) 43 (19.8) 43 (21.4) 0.4 Donor CMV (%) Recipient CMV (%) Diabetes (%) Black donor (%) NOTE: Data are presented as means (standard deviation). Abbreviations: BMI, body mass index; CMV, cytomegalovirus; INR, international normalized ratio. *HCV-negative white transplant recipients versus HCV-negative black transplant recipients. ischemia time, and donor diabetes mellitus status were not found to be significant predictors of outcome and were consequently not included in the multivariate analysis. When the regression analysis was limited to only post-meld transplants, having a graft from a white donor was again found to be an independent risk factor for graft failure among HCV-positive black recipients (HR 1.47, P 0.007). In contrast, a Cox regression analysis of HCV-negative black recipients did not find that having a graft from a white donor was an independent risk factor for graft failure (HR 0.89, P not significant). Thus, HCV appears to be an effect modifier: only in HCV-infected black recipients is a white donor associated with an increased risk of graft failure. This was formally tested with the Breslow-Day statistic for heterogeneity. As expected, significant heterogeneity in graft survival was seen among black recipients when donor-recipient mismatch was stratified by the presence or absence of HCV (P 0.003). To further investigate this interaction, we constructed a combined model that included 2-way and 3-way interaction terms among race, HCV status, and mismatch. Each one of these main effects was a significant predictor of mortality, as was the 3-way interaction term (P 0.002); this suggests that the combination of black race, HCV positive status, and donor/ recipient race mismatch is particularity deleterious. Regression coefficients, HRs, and P values are shown in Supporting Table 1. When the aforementioned regression analyses were then repeated, including all records and using single imputation for all missing variables, the previous observations remained significant; this suggests that any impact from missing data was minimal. To address the potential role of HLA mismatch in these observations, we performed a comparison of the degree of HLA mismatch (A, B, and DR loci) between HCV-positive recipients with black donors and those with white donors (Fig. 3). Among black recipients, having a black donor versus a white donor did not alter the statistical likelihood of having any degree of recipientdonor mismatch at the HLA loci tested. Specifically, the null hypothesis was not rejected when Fisher s exact test was used to examine the proportion of HCV-positive black recipients with black donors versus white donors at HLA match levels of 2/6 (P 0.54), 3/6 (P 0.18), and 4/6 (P 0.55). Thus, the observed difference in outcome between HCV-positive black recipients with black donors and those with white donors cannot be attributed, per se, to simple HLA mismatch at the A, B, and DR loci. A limitation of this analysis is that the HLA type for both the recipient and donor was available in only 46% of HCV-positive transplant cases; the frequency of missing data, however, was similar across the different donor/recipient race combinations. We also examined the causes of death in black and white donors, including stroke, head trauma, and central nervous system tumors. Blacks were more likely to have died from cerebrovascular accident or stroke (CVA) than whites (49% versus 44%, P 0.001). Whites were more likely to have died from head trauma than blacks (43% versus 38%, P 0.001). In univariate analysis, only donor death from CVA was found to be a risk factor for posttransplant mortality. However, CVA was not found to be a risk factor in multivariate analysis. This was not unexpected because donors who died from CVA tended to be older than those who died from other causes, and thus the apparent effect of this particular cause of death is approximated by donor age, for which there was no difference between black and white recipients (P 0.24, Table 1), Thus, cause of death does not appear to be an independent factor that explains our

5 1130 PANG, KAMAL, AND GLENN Figure 2. Kaplan-Meier graft survival curves. (A) HCV-positive liver transplant recipients by recipient-donor race and (B) HCV-negative liver transplant recipients by recipient-donor race. The number of patients at risk in each cohort is indicated. Abbreviation: HCV, hepatitis C virus. observations. This is also consistent with our initial observations: we found that donor-recipient mismatch plays a significant role in HCV-positive recipients, but not in HCV-negative recipients, and yet because both cohorts would be expected to have donors with similar causes of death, donor cause of death is an unlikely explanation for these observations. DISCUSSION This study shows that black patients who are HCVpositive and undergo liver transplantation have improved graft survival if their donor is black. Cox regression analysis determined that among HCV-positive black recipients, having a black donor is an independent predictor of graft survival. The observed increase in graft survival due to recipient-donor race matching is notably specific to black transplant recipients infected with HCV. Moreover, simple HLA mismatch at the A, B, and DR loci, per se, did not appear to be responsible for the decreased survival of HCV-positive black recipients who had white donors, as no statistical difference in the degree of HLA mismatch was found between HCV-positive black recipients with black donors and those with white donors. Nevertheless, it is quite possible that database limitations, more subtle differences at these genetic loci, or other immune-related genetic loci played a role in the outcomes observed here. 9,10 It has been previously observed that a black donor is associated with a lower graft survival rate. 7,11 This result is not contradictory to our analysis. We also show that having a black donor is an independent predictor of graft failure, but specifically within the white cohort that makes up the large majority of the transplant population. The magnitude of this effect, however, was smaller (HR 1.13) and not specific to HCV-infected patients; furthermore, differences in the degree of HLA match among white recipients complicates the interpretation of this result. Also notable is the study by Nair and Thuluvath, 12 who analyzed donor-recipient race mismatch in an exclusively pre-meld cohort ( ). This smaller study analyzed graft survival at 2 years and concluded that black recipients with black donors fared marginally worse than those with white donors. As this study did not stratify by HCV status, a direct comparison cannot be made. Nevertheless, in our HCV-negative cohort, we also observed a difference in graft survival at 2 years similar to that seen by Nair and Thuluvath, but this difference became largely immaterial by year 5 (Fig. 2B). The reason for the improved graft survival conferred by race-matched grafts in HCV-positive black recipients is not clear. Because of the large number of patients (49.8%) with incompletely recorded, multifactorial, or indeterminate causes of death, we can only speculate on potential factors that may or may not be responsible. We note that the Kaplan-Meier curves for HCV-positive black recipients with black donors versus white donors diverge by as early as 1 year and continue to further diverge thereafter (Fig. 2A). This suggests that the processes responsible for this difference in survival are ongoing ones and are not likely solely related to the immediate posttransplant period. Similarly, incomplete data precluded an analysis of viral recurrence or rejection rates or a comparison of immunosuppression regimens. Nevertheless, our results suggest that a genetic component plays a role in HCV-positive black transplant recipient outcomes, as opposed to the outcome being determined entirely by demographic factors, given that HCV-positive black transplant recipients are likely to be demographically similar to one another, regardless of whether their donors are white or black. A number of possible processes may be responsible for these outcome differences, including an increased inflammatory response in the presence of HCV or suboptimal control of viral replication. For example, stud-

6 DONOR RACE AND SURVIVAL OF BLACK AMERICANS 1131 TABLE 3. Multivariate Cox Regression Analysis for Risk of Graft Failure: HRs for Donor/Recipient Race Mismatch HCV-Positive Black Recipients P (95% CI) Value Regression Analysis Cohorts* HCV-Negative Black Recipients (95% CI) P Value Race-matched donor 1 1 Race-unmatched donor 1.41 ( ) ( ) HCV-Positive White Recipients P (95% CI) Value HCV-Negative White Recipients (95% CI) P Value Race-matched donor 1 1 Race-unmatched donor 1.13 ( ) ( ) Abbreviations: CI, confidence interval; HCV, hepatitis C virus; HR, hazard ratio. *Separate regression analyses were performed on each of the 4 transplant cohorts to determine the risk attributable to a race-unmatched graft. Adjusted for donor age, recipient age, cold ischemia time, serum creatinine, serum bilirubin, diabetes mellitus, body mass index, and donor cytomegalovirus status. The percentages of usable observations (patients included in the multivariate analysis; others were excluded because of missing data) were as follows: 86% for HCV-positive blacks, 79% for HCV-negative blacks, 85% for HCV-positive whites, and 82% for HCV-negative whites. Figure 3. Degree of HLA match between recipients and donors in HCV-infected liver transplant patients. The cumulative percentage of patients by HLA match (A, B, and DR loci) is illustrated in the bar graphs (top) from a 6/6 match (left) to a 0/0 match (right). Actual percentages are given in the table. *P for an HLA match level > 3/6 with Fisher s exact test; **P for an HLA match level > 3/6 with the chi-squared statistic (this was necessary because of the large number of white transplant patients). See the text for additional statistics. Abbreviations: HCV, hepatitis C virus; HLA, human leukocyte antigen. ies suggest that HCV can down-regulate natural killer (NK) cell activity 13 ; in turn, NK activity has been shown to correlate with the clearance of HCV. 14 Thus, genetic differences in NK receptors, which have been shown to vary by race, 10 may account for the positive effect of having a black donor that has been observed specifically in the context of black recipients transplanted for chronic hepatitis C. As the liver is also an immunoprivileged organ with a key role in tolerance and T cell apoptosis, 15 other immune pathways may be involved as well. More detailed data sets and further laboratory studies are necessary to address these questions. Another possibility is a silent infection carried by the graft that affects posttransplant HCV pathogenesis, such as a latent hepatotropic virus. CMV serostatus, however, was not found to account for the deleterious affect of Caucasian grafts in HCV-positive African Americans. Insufficient data existed to examine the role of Epstein-Barr virus or other herpes viruses. Because of database limitations, donor steatosis was not included in our regression analysis. Donor steatosis has previously been shown to decrease graft survival. 8 However, it appears unlikely that this factor is confounding our analysis. The risk factors for steatosis include diabetes mellitus and obesity, both of which are more common among blacks. Thus, if any effect was observed by controlling for donor steatosis, it might actually be to increase the positive effect attributable to placing race-matched grafts in HCV-positive black transplant patients. Notably, the number of black recipients with black donors who had follow-up data for 5 or more years (n 44) was relatively small (Fig. 2A). Despite this small number, however, statistical significance was achieved both in the Kaplan-Meier analysis/log-rank test and in our regression analysis, and this suggests that the strength of the observation was substantial. Furthermore, the observation that the curve for HCV-positive black recipients with white donors diverges from that for those with black donors by as early as 1 year and in

7 1132 PANG, KAMAL, AND GLENN a statistically significant manner, when 200 black transplant recipients remain in the analysis, also provides support for the clinical relevance of these observation (Fig. 2A). Although preliminary, this retrospective study has found a notable survival advantage in HCV-positive black transplant recipients whose donors are black. The mechanism underlying this effect and its HCVspecific nature remain an area for future research. Additionally, case series that are able to detail graft failure due to rejection versus viral recurrence as a function of donor and recipient race, while addressing immunosuppressive regimens, are likely to shed further light on this matter. Of note, posttransplant treatment of HCVinfected patients is now increasingly common. 16 As the number of treated patients increases, the ability to study the role of donor-recipient race mismatch on posttransplant treatment outcome might also shed new light on the relative role of the liver itself and its response to the immune system versus the role of the host immune system in response to interferon therapy. Interestingly, a single-center experience with pediatric heart transplants recently demonstrated that black recipients with black donors fared better than those who had white donors. 17 An analysis of UNOS-derived data of deceased kidney organ transplantation also found that black recipients with black donors fared better than those who had white donors. 18 In conclusion, this study suggests that race mismatch appears to play a significant role in the low rate of graft survival seen among HCV-positive blacks; this observation may ultimately provide insight into the genetic and nongenetic factors that govern host control of HCV and liver transplant outcomes. ACKNOWLEDGMENT The authors thank Dr. Emmet Keeffe, Dr. Dolly Tyan, Dr. Edgar Engleman, Dr. Samuel Strober, and Dr. Julie Parsonnet for their careful review and thoughtful comments; Dr. Valaiporn Rusmintratip for assistance with the manuscript preparation; and the United Network for Organ Sharing for providing transplant data. REFERENCES 1. Moylan CA, Brady CW, Johnson JL, Smith AD, Tuttle- Newhall JE, Muir AJ. Disparities in liver transplantation before and after introduction of the MELD score. JAMA 2008;300: Nair S, Eustace J, Thuluvath PJ. Effect of race on outcome of orthotopic liver transplantation: a cohort study. Lancet 2002;359: Pyrsopoulos N, Jeffers L. Hepatitis C in African Americans. J Clin Gastroenterol 2007;41: Ioannou GN. Development and validation of a model predicting graft survival after liver transplantation. Liver Transpl 2006;12: Verna EC, Brown RS Jr. Hepatitis C virus and liver transplantation. Clin Liver Dis 2006;10: Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 2002;122: Feng S, Goodrich NP, Bragg-Gresham JL, Dykstra DM, Punch JD, DebRoy MA, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant 2006;6: Berenguer M. Risk of extended criteria donors in hepatitis C virus-positive recipients. Liver Transpl 2008;14(suppl 2):S45 S Gane EJ. The natural history of recurrent hepatitis C and what influences this. Liver Transpl 2008;14(suppl 2):S36 S Norman PJ, Abi-Rached L, Gendzekhadze K, Korbel D, Gleimer M, Rowley D, et al. Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans. Nat Genet 2007;39: Rustgi VK, Marino G, Halpern MT, Johnson LB, Umana WO, Tolleris C. Role of gender and race mismatch and graft failure in patients undergoing liver transplantation. Liver Transpl 2002;8: Nair S, Thuluvath PJ. Does race-matched liver transplantation offer any graft survival benefit? Transplant Proc 2001;33: Golden-Mason L, Rosen HR. Natural killer cells: primary target for hepatitis C virus immune evasion strategies? Liver Transpl 2006;12: Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 2004;305: Crispe IN. Hepatic T cells and liver tolerance. Nat Rev Immunol 2003;3: Roche B, Sebagh M, Canfora ML, Antonini T, Roque- Afonso AM, Delvart V, et al. Hepatitis C virus therapy in liver transplant recipients: response predictors, effect on fibrosis progression, and importance of the initial stage of fibrosis. Liver Transpl 2008;14: Kanter KR, Berg AM, Mahle WT, Vincent RN, Kilgo PD, Kogon BE, Kirshbom PM. Donor-recipient race mismatch and graft survival after pediatric heart transplantation. Ann Thorac Surg 2009;87: ; discussion Locke JE, Warren DS, Dominici F, Cameron AM, Leffell MS, McRann DA, et al. Donor ethnicity influences outcomes following deceased-donor kidney transplantation in black recipients. J Am Soc Nephrol 2008;19: