Dig Dis Sci (2010) 55:883–889 DOI 10.1007/s10620-009-0803-7
REVIEW
Liver Transplantation in the Ethnic Minority Population: Challenges and Prospects Nyingi Kemmer Æ Guy W. Neff
Received: 4 January 2009 / Accepted: 17 March 2009 / Published online: 24 April 2009 Ó Springer Science+Business Media, LLC 2009
Abstract In the USA, end-stage liver disease (ESLD) is a major cause of morbidity and mortality among ethnic minorities. Ethnic populations vary with respect to chronic liver disease prevalence, access to transplantation, and therapeutic outcomes post liver transplantation. These ethnic differences present unique challenges to healthcare professionals involved in the care of patients with chronic liver disease prior and post transplantation. This review will discuss the variations and challenges of liver transplantation in the ethnic minority population. Keywords
Ethnicity Liver transplantation
Abbreviations ESLD End-stage liver disease MELD Model for end-stage liver disease HCV Hepatitis C virus OPTN Organ Procurement and Transplantation Network UNOS United Network for Organ Sharing LT Liver transplantation
Since the introduction of orthotopic liver transplantation about four decades ago, there has been a steady improvement in long-term survival as a result of new and evolving immunosuppressive therapies, and the application of novel surgical techniques. Consequently, liver transplantation is now accepted as the curative therapeutic modality for N. Kemmer (&) G. W. Neff University of Cincinnati, MSB Room 6363, 231 Albert Sabin Way, Cincinnati, OH 45267-0595, USA e-mail:
[email protected] N. Kemmer Cincinnati VA Medical Center, Cincinnati OH, USA
individuals with ESLD. In the USA, ESLD is a major cause of morbidity and mortality among ethnic minorities. Ethnic populations vary with respect to chronic liver disease prevalence, access to transplantation, and therapeutic outcomes post liver transplantation. These ethnic differences present unique challenges to healthcare professionals involved in the care of patients with ESLD. This review will discuss the variations and challenges of liver transplantation in the ethnic minority population.
Prevalence and Disease Burden In the USA, hepatitis C and hepatocellular carcinoma (HCC) are the two most frequent indications for liver transplantation. These diseases disproportionately affect ethnic minorities. In fact, the prevalence of hepatitis C is twofold higher in African Americans when compared with Caucasians and Hispanics (3% compared with 1.5% and 1.3%, respectively). Additionally, the response to interferon-based therapy for the most common hepatitis C virus (HCV) genotype-1 is lower in African Americans and Hispanics than in Caucasians. Not surprisingly, recent data from the National Center for Health Statistics revealed an ethnic difference in hepatitis C-related mortality [1–4]. In regards to HCC, several epidemiologic studies have documented higher prevalence of HCC among ethnic minorities [5, 6]. Reports also suggest that, at time of clinical presentation, ethnic minorities, and in particular African Americans, are more likely to have progressed to an advanced stage (beyond Milan criteria) and are thus ineligible for liver transplantation [7]. The exact reason for this variation in disease severity at presentation is unclear and warrants further investigation. Although the vast majority of patients with HCC have underlying hepatitis C virus
123
884
Dig Dis Sci (2010) 55:883–889
(HCV) infection, there is no direct correlation between ethnicity and nonresponsiveness to antiviral therapy and aggressive hepatoma. Liver disease severity, and particularly nonresponsiveness to therapy, is of concern in those with autoimmune liver diseases. Recent studies have shown that, prior to liver transplantation, primary biliary cirrhosis and autoimmune hepatitis are more aggressive in African Americans and have decreased response to available therapies [8, 9]. Because the implications for transplantation outcome are significant, it is critical to understand these ethnic variations in disease severity and therapeutic response prior to liver transplantation.
Access to Liver Transplantation In the USA, organ allocation for liver transplantation is dependent on disease severity and can vary depending upon geographic location. Liver disease severity and geographic location are based on the model for end-stage liver disease (MELD), and the United Network for Organ Sharing (UNOS) regions, respectively. The goal of this allocation system was to assign priority to the sickest candidates and to assure equitable access to transplantation. Since its adoption in February 2002, there has been a reduction in waiting list mortality as well as an increase in transplantation rate. Unfortunately, despite these successes of the MELD allocation system, unequal distribution of a limited pool of organs for transplantation continues to exist, and ethnic minorities suffer from a notable disparity in access to liver transplantation. The trend of liver transplantation and ethnic distribution of recipients in the USA in the last decade is shown in Fig. 1. Liver transplant initiation involves a stepwise approach beginning with referral to the transplant center, evaluation for transplant candidacy, placement on the waiting list, and finally receipt of an organ. The disparity in access to liver transplantation for ethnic minorities has been attributed to impediments during the initial steps of the activation process. This report will address various areas
Fig. 1 Liver transplantation www.unos.org
123
trends
among
ethnic
groups
that reveal potential discrepancies in access among ethnic groups. Utilization of Liver Transplantation Ethnic disparities in healthcare resource utilization are well documented. In liver transplantation, Nguyen et al. recently found that transplantation was lower in Hispanics and African Americans when compared with Caucasians, a finding similar to a report by Reid and colleagues, demonstrating underrepresentation of African Americans among adult liver transplant recipients [10, 11]. Of interest, Neff et al. [12] reported a higher proportion of ethnic minorities among pediatric liver transplant recipients in comparison with adult recipients (43.3% versus 23.9%, respectively), suggesting that reduced utilization of transplant services was more pronounced in adults. Despite the underrepresentation of ethnic minorities among adult liver transplant recipients, the transplantation rate is similar irrespective of ethnicity among patients on the waiting list. Thus the disparity is not within the transplant network (UNOS/OPTN), and is unrelated to the MELD allocation system. Rather, the disparity appears to be related to other factors including lack of sufficient health insurance, poor referral patterns, and geographic location. Referral Pattern and Health Insurance Appropriate referral to an organ transplant center is the initial step in the evaluation process for liver transplantation. Therefore, a delay in referral or lack of referral of ESLD patients to a transplant center is a potential barrier to liver transplantation. Severity of disease at time of referral to a transplant center is only a crude marker of referral patterns, but in the absence of prospective studies, is the best available indicator. In a multicenter US-based study, Lee et al. [13] recently reported that African Americans were referred for transplantation at a higher MELD compared with other ethnic groups, suggesting delayed referral. Eckhoff et al. [14], in a single-center study, also found that ethnic minorities appeared to be associated with delayed referral for liver transplantation. The exact reason for delayed referral among ethnic minorities was not identified in these studies, and the impact of the individual’s health insurance was not determined. Nguyen and colleagues, in a large retrospective study of individuals with ESLD, identified private insurance as an independent predictor of likelihood of liver transplantation [10]. This retrospective study was not designed to evaluate the interaction between insurance and referral pattern in relation to likelihood of liver transplantation. However, a recent study by Julapalli et al. [15] addressed the issue of insurance and referral pattern, and found that in Veterans Affairs hospitals where
Dig Dis Sci (2010) 55:883–889
all patients have insurance, Black race was an independent factor for lack of transplant referral among patients who met the medical criteria for liver transplantation. Thus, even in the presence of universal health insurance, there was an ethnic difference in referral that had the effect of limiting access to liver transplantation. Interestingly, a UK study revealed that, even in a system with universal health insurance, geographic proximity to a transplant center was an additional factor limiting accessibility [16]. Geographic Location In recent years, the primary research areas of interest in relation to liver transplantation access have focused on disease severity (based on MELD), waiting time, transplant center volume, and donation service areas [17, 18]. These factors reflect the efficiencies of the transplantation network (UNOS/OPTN) and the MELD allocation system. Access issues that are external to the transplantation network, with the exception of socioeconomic status, have received minimal attention in the liver transplantation literature [19]. In the USA, the influence of geographic location on the initial step of the liver transplant activation process was the focus of two studies, although neither specifically addressed ethnic minorities. In the first study, which was a single-state-based time-series analysis of access to liver transplantation, the investigators found that rural county of residence and distance from center were associated with rates of transplantation, but the strongest association was the payor source [20]. Although patient demographics such as age and gender were assessed, ethnicity or race was not included in the analysis. The second study, by Ellison et al. [21], addressed geographic variability at the regional level with emphasis on allocation policies and organ procurement organization centers. The implications of the observed geographic variability on the ethnic minority population were not addressed. However, in a recent study, we reported that significant variations in access to liver transplantation for ethnic minorities exist across geographic lines, which was not consistent with the ethnic composition of the respective geographic region [22] (Fig. 2). The role of spatial accessibility, which refers
885
to travel impedance (i.e., distance from transplant center), and availability of transplant centers was not assessed in this study. Firozvi et al. [23], in a recent study, did not find a significant effect of travel time on differences in clinical outcomes post transplantation, but the study was not designed to address ethnicity-specific issues. In contrast, Axelrod et al. [24] reported that a greater proportion of ethnic minorities tend to reside in urban regions, where transplant centers are typically located. This suggests that distance may not be the key barrier to access among ethnic minorities in specific geographic locations. Disparity in Transplantation Outcomes Several studies have reported ethnic variations in long-term outcomes among liver transplant recipients. The disparate outcomes observed among ethnic minorities involve several aspects of posttransplant care that in some cases are disease specific and partly influenced by immunosuppressive therapy. In general, short- and long-term survival of adult liver transplant recipients is decreased in ethnic minorities. In particular there is a disproportionate decrease in patient and graft survival among African Americans in comparison with Caucasians and Hispanics [12, 25] (Table 1). Although, the Asian population accounts for 4.4% of the US population, there is limited information on transplantation trends for this ethnic group. A recent study analyzed data from the UNOS registry (1998–2007), showing a significant difference in patient and graft survival for Asians in comparison with non-Asians, with 5-year survival of 71%, 68%, 67%, and 57% for Asians, Hispanic, Caucasian, and African Americans, respectively [26]. Of interest, a recent study based on clinical data obtained from four high-volume US liver transplant centers found no ethnic difference in either patient or graft survival [13]. The reason for this discrepancy with other published
Table 1 Kaplan–Meier patient survival/graft survival for adult recipients (P B 0.001) [12] Year
Black (%)
Hispanic (%)
White (%)
Other (%)
Kaplan–Meier patient survival 1 84 87
87
87
3
72
79
80
80
5
65
73
73
75
10
51
60
57
64
Kaplan–Meier graft survival
Fig. 2 Liver transplantation trends: ethnicity and UNOS region [22]
1
78
82
82
82
3
65
73
73
74
5
57
67
67
69
10
43
53
51
59
123
886
studies is unclear. The investigators state it is unrelated to sample size and postulate that the discrepancy could be attributed to unequal access to high-quality liver transplant centers. Though the report also found a disproportionately higher proportion of recipients with a diagnosis of fulminant hepatic failure among African Americans (14.8%) in comparison with Caucasians (4.1%) and others (5.8%), this did not appear to play a role in overall survival. With the improvement in survival outcomes, there has been a growing interest in the functional and physical wellbeing of liver transplant recipients. Several studies have shown a significant benefit in health-related quality of life (HRQOL) measures post liver transplantation [27, 28]. Though there are studies suggesting decreased benefit in several domains of HRQOL measures among ethnic minorities receiving post-kidney transplantation, comparable data is lacking in liver transplant literature [29, 30]. Disease-Specific Effects Ethnic differences in chronic liver disease are well documented but the impact of these differences on long-term survival post liver transplantation have not been well established [31]. Chronic hepatitis C is the most frequent indication for adult liver transplantation. Although HCV recurrence post transplantation is universal, severity and disease progression are variable. Several studies have implicated ethnicity as a predictor of long-term survival in these patients. Charlton et al. [32] identified recipient race as a predictor in the HCV subgroup. Similarly, Velidedeoglu et al. [33] found recipient race was an independent predictor of survival in recipients with HCV. There was no significant difference in survival for non-HCV recipients based on ethnicity, suggesting that the disparity in survival observed in African Americans may be related to the presence of hepatitis C. In view of the fact that sustained virologic response (SVR) to interferon-based therapy is associated with lower mortality in transplant recipients [34], the decreased survival may, in part, be related to the decreased response rates in African Americans. Although *50% of cases of HCC are related to HCV, concomitant HCC does not have a significant impact on long-term survival. In particular, in the study by Bozorgzadeh et al., the survival rates for recipients with HCV alone were comparable to those with HCV and concomitant HCC, suggesting that HCC had no independent impact in patients with underlying hepatitis C [35]. The impact of ethnicity in patients with HCV and concomitant HCC in respect to liver transplantation is yet to be determined. The impact of ethnicity on posttransplant survival in patients with autoimmune liver disease is another area of concern. Three autoimmune diseases commonly seen in
123
Dig Dis Sci (2010) 55:883–889
adult liver transplant recipients—autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis—occur more frequently among ethnic minorities. Among liver transplant recipients, primary sclerosing cholangitis and autoimmune hepatitis occur more frequently in African Americans, while primary biliary cirrhosis is more common in Hispanics than in other ethnic groups [25, 36]. The exact interaction between genetic susceptibility to autoimmune liver disease, therapeutic response, and prognosis among ethnic minority transplant recipients is yet to be determined. Immunosuppression The effect of immunosuppressive therapy as an independent factor on posttransplant survival is an evolving area of investigation. Despite the paucity of randomized controlled trials focusing on this area, most immunosuppressive strategies have been individualized, with particular attention to the underlying liver disease. For instance, recipients with autoimmune hepatitis are treated with more immunosuppression, but HCV recipients are treated with minimal immunosuppression. The effect of ethnicity on the pharmacokinetics of commonly used immunosuppressive agents in liver transplant recipients has not been established. Current immunosuppressive drugs for maintenance therapy in liver transplantation include corticosteroids, calcineurin inhibitors (Cyclosporine and Tacrolimus), antimetabolites (Mycophenolate), and mammalian target of rapamycin inhibitor (Sirolimus). In a study focusing on ethnicity, immunocompetence was evaluated in African Americans and Caucasians [37]. The investigators used in vitro tests of immunocompetence to measure the effects of immunosuppression in transplant recipients and found that, among patients receiving a tacrolimus-based regimen, African Americans had a reduced immunosuppressive effect in comparison with Caucasians. The enhanced immune responsiveness in African Americans is thought to contribute to the increased risk of allograft rejection in transplant recipients. In another trial focusing on pharmacokinetics, the investigators found that bioavailability of cyclosporine was reduced 20–50% in African Americans compared with other ethnic groups, resulting in a higher dose requirement to reach a given trough level [38]. Published reports on the impact of ethnicity on the newer immunosuppressive agents (Mycophenolate and Sirolimus) have been equivocal [38–40]. As we seek strategies to improve long-term outcomes among ethnic minorities, the currently available data with respect to immunosuppressive therapy in liver transplantation indicate that it would be prudent to integrate pharmacogenomic considerations into current and future immunosuppressive protocols.
Dig Dis Sci (2010) 55:883–889
887
Allograft Function Among ethnic minorities, the effect of the observed immune hyperresponsiveness on short- and long-term allograft function is of interest. Although, several studies have shown African American ethnicity to be independently associated with acute cellular and chronic graft rejection, the exact incidence is yet to be defined [41, 42]. Although no direct correlation with immunologic risk is known to exist, immune responsiveness is presumed to play a major role. The role of human leukocyte antigen (HLA) matching on graft viability in ethnic minorities is yet to be determined. Although none of the studies have focused on HLA matching among ethnic minority liver transplant recipients, it is clear from the existing literature that HLA matching has no significant impact on hepatic allograft survival, a finding that is in contrast to that in kidney transplantation [43–45]. Similarly, among recipients of extended criteria donor organs, ethnicity was not found to be associated with early graft failure, though its impact on late graft failure is unknown [46]. In a recent study, liver transplant recipients with primary sclerosing cholangitis, primary biliary cirrhosis, and autoimmune hepatitis had a higher incidence of late acute rejection ([3 months post transplant), and patients with late acute rejection had significantly lower patient and graft survival [47]. Since these autoimmune diseases occur more frequently in ethnic minorities, the implication of this finding requires further investigation in this population.
Other Issues Organ Donation The widening gap between organ supply and the demand for transplantation is of great concern to the transplant community. The disparity in organ donation (deceased and living) is more pronounced among ethnic minorities. The shortage of organ donation among ethnic minorities is in part a function of sociodemographic factors, cultural attitudes, distrust of the medical community, and religious beliefs [48, 49]. Improving organ availability, and particularly increasing the organ donation rate among ethnic minorities, are national health priorities. One of the programs created to address the disproportionate under representation among organ donors is the Minority Organ Tissue Transplant Education Program (MOTTEP). This program has helped educate minorities in the country about organ donation. Recently, the initiation of the Organ Donation Breakthrough Collaboration by the Division of Transplantation at the Health Resources and Services Administration has led to a notable increase in the organ donor pool. The recent OPTN/ SRTR report on organ donation and utilization shows
Fig. 3 Organ donation rates by ethnicity www.unos.org
increasing organ donation rates, especially among ethnic minorities (Fig. 3). Continued efforts to increase organ donation at the national level is a useful strategy to narrow the gap between organ donation in ethnic and non-ethnic minorities.
Conclusion This review discusses the various challenges encountered in the ethnic minority population. In this era of organ transplantation, the significance of adequate representation of currently underrepresented ethnic minorities in clinical trials involving transplant outcomes and organ donation cannot be overemphasized. In order to benefit from clinical research, the active participation of ethnic minorities is essential if the results of these studies are to be applicable to them. In view of our ethnically diverse population, heightened awareness and understanding of ethnic variations in liver disease prevalence and clinical presentation are important as we continue to engage in the evaluation of patients for liver transplantation. As well, awareness of sociocultural differences and training in cultural competency are necessary skill sets for healthcare providers participating in the transplant evaluation process. The challenges discussed in this article illustrate the complex relationship between ethnicity and health/healthcare disparity with respect to accessibility, affordability, and quality of liver transplantation. A better understanding of this relationship promises to identify strategies to improve transplantation access, increase organ donation, decrease the prevalence of preventable liver disease, and ultimately improve therapeutic outcomes among ethnic minorities.
References 1. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006; 144:705–714.
123
888 2. Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. 2004;350:2265–2271. doi: 10.1056/NEJMoa032502. 3. Cheung RC, Currie S, Shen H, et al. Chronic hepatitis C in Latinos: natural history, treatment eligibility, acceptance, and outcomes. Am J Gastroenterol. 2005;100:2186–2193. doi:10.1111/j.15720241.2005.00240.x. 4. Wise M, Bialek S, Finelli L, Bell BP, Sorvillo F. Changing trends in hepatitis C-related mortality in the United States, 1995–2004. Hepatology. 2008;47(4):1128–1135. 5. El-Serag HB, Lau M, Eschbach K, Davila J, Goodwin J. Epidemiology of hepatocellular carcinoma in Hispanics in the United States. Arch Intern Med. 2007;167:1983–1989. doi:10.1001/ archinte.167.18.1983. 6. El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002;35:S72–S78. doi:10.1097/00004836200211002-00002. 7. Kemmer N, Neff G, Secic M, Zacharias V, Kaiser T, Buell J. Ethnic differences in hepatocellular carcinoma: implications for liver transplantation. Dig Dis Sci. 2007;53(2):551–555. 8. Peters MG, Di Bisceglie AM, Kowdley KV, et al. Differences between Caucasian, African American, and Hispanic patients with primary biliary cirrhosis in the United States. Hepatology. 2007;46:769–775. doi:10.1002/hep.21759. 9. Verma S, Torbenson M, Thuluvath PJ. The impact of ethnicity on the natural history of autoimmune hepatitis. Hepatology. 2007; 46:1828–1835. doi:10.1002/hep.21884. 10. Nguyen GC, Segev DL, Thuluvath PJ. Racial disparities in the management of hospitalized patients with cirrhosis and complications of portal hypertension: a national study. Hepatology. 2007;45:1282–1289. doi:10.1002/hep.21580. 11. Reid AE, Resnick M, Chang Y, Buerstatte N, Weissman JS. Disparity in use of orthotopic liver transplantation among blacks and whites. Liver Transpl. 2004;10:834–841. doi:10.1002/lt.20174. 12. Neff GW, Kemmer N, Kaiser T, Zacharias V, Majoras N, Safdar K. Outcomes in adult and pediatric liver transplantation among various ethnic groups. Transplant Proc. 2007;39:3204–3206. doi: 10.1016/j.transproceed.2007.09.031. 13. Lee TH, Shah N, Pedersen RA, et al. Survival after liver transplantation: is racial disparity inevitable? Hepatology. 2007;46: 1491–1497. doi:10.1002/hep.21830. 14. Eckhoff DE, McGuire BM, Young CJ, et al. Race: a critical factor in organ donation, patient referral and selection, and orthotopic liver transplantation? Liver Transpl Surg. 1998;4:499–505. doi: 10.1002/lt.500040606. 15. Julapalli VR, Kramer JR, El-Serag HB. Evaluation for liver transplantation: adherence to AASLD referral guidelines in a large veterans affairs center. Liver Transpl. 2005;11:1370–1378. doi:10.1002/lt.20434. 16. McCormick PA, O’Rourke M, Carey D, Laffoy M. Ability to pay and geographical proximity influence access to liver transplantation even in a system with universal access. Liver Transpl. 2004;10:1422–1427. doi:10.1002/lt.20276. 17. Ahmad J, Bryce CL, Cacciarelli T, Roberts MS. Differences in access to liver transplantation: disease severity, waiting time, and transplantation center volume. Ann Intern Med. 2007;146:707–713. 18. Barshes NR, Becker NS, Washburn WK, Halff GA, Aloia TA, Goss JA. Geographic disparities in deceased donor liver transplantation within a single UNOS region. Liver Transpl. 2007;13:747–751. doi: 10.1002/lt.21158. 19. Yoo HY, Galabova V, Edwin D, Thuluvath PJ. Socioeconomic status does not affect the outcome of liver transplantation. Liver Transpl. 2002;8:1133–1137. doi:10.1053/jlts.2002.37000. 20. Tuttle-Newhall JE, Rutledge R, Johnson M, Fair J. A statewide, population-based, time series analysis of access to liver
123
Dig Dis Sci (2010) 55:883–889
21.
22.
23.
24.
25.
26. 27.
28.
29.
30.
31. 32.
33.
34.
35.
36.
37.
38.
transplantation. Transplantation. 1997;63:255–262. doi:10.1097/ 00007890-199701270-00014. Ellison MD, Edwards LB, Edwards EB, Barker CF. Geographic differences in access to transplantation in the United States. Transplantation. 2003;76:1389–1394. doi:10.1097/01.TP.00000 90332.30050.BA. Kemmer N, Safdar K, Kaiser T, Zacharias V, Neff GW. Impact of geographic location on access to liver transplantation among ethnic minorities. Transplantation. 2008;85:166–170. doi:10.1097/ TP.0b013e31816223f8. Firozvi AA, Lee CH, Hayashi PH. Greater travel time to a liver transplant center does not adversely affect clinical outcomes. Liver Transpl. 2008;14:18–24. doi:10.1002/lt.21279. Axelrod DA, Guidinger MK, Finlayson S, et al. Rates of solidorgan wait-listing, transplantation, and survival among residents of rural and urban areas. JAMA. 2008;299:202–207. doi:10.1001/ jama.2007.50. Nair S, Eustace J, Thuluvath PJ. Effect of race on outcome of orthotopic liver transplantation: a cohort study. Lancet. 2002;359:287–293. doi:10.1016/S0140-6736(02)07494-9. Kemmer N. Liver transplantation trends and survival in the Asian population. Hepatology. 2008;48:568A. Tome S, Wells JT, Said A, Lucey MR. Quality of life after liver transplantation. A systematic review. J Hepatol. 2008;48:567– 577. doi:10.1016/j.jhep.2007.12.013. Bravata DM, Olkin I, Barnato AE, Keeffe EB, Owens DK. Health-related quality of life after liver transplantation: a metaanalysis. Liver Transpl Surg. 1999;5:318–331. doi:10.1002/lt.50 0050404. Johnson CD, Wicks MN, Milstead J, Hartwig M, Hathaway DK. Racial and gender differences in quality of life following kidney transplantation. Image J Nurs Sch. 1998;30:125–130. doi:10.1111/ j.1547-5069.1998.tb01266.x. Bakewell AB, Higgins RM, Edmunds ME. Does ethnicity influence perceived quality of life of patients on dialysis and following renal transplant? Nephrol Dial Transplant. 2001;16: 1395–1401. doi:10.1093/ndt/16.7.1395. Kemmer N, Neff GW. Ethnic variations in chronic liver diseases. Dig Dis Sci. 2008;53(5):1339–1344. Charlton M, Seaberg E, Wiesner R, et al. Predictors of patient and graft survival following liver transplantation for hepatitis C. Hepatology. 1998;28:823–830. doi:10.1002/hep.510280333. Velidedeoglu E, Mange KC, Frank A, et al. Factors differentially correlated with the outcome of liver transplantation in HCV? and HCV- recipients. Transplantation. 2004;77:1834–1842. doi: 10.1097/01.TP.0000130468.36131.0D. Picciotto FP, Tritto G, Lanza AG, et al. Sustained virological response to antiviral therapy reduces mortality in HCV reinfection after liver transplantation. J Hepatol. 2007;46:459–465. doi: 10.1016/j.jhep.2006.10.017. Bozorgzadeh A, Orloff M, Abt P, et al. Survival outcomes in liver transplantation for hepatocellular carcinoma, comparing impact of hepatitis C versus other etiology of cirrhosis. Liver Transpl. 2007;13:807–813. doi:10.1002/lt.21054. Maheshwari A, Yoo HY, Thuluvath PJ. Long-term outcome of liver transplantation in patients with PSC: a comparative analysis with PBC. Am J Gastroenterol. 2004;99:538–542. doi:10.1111/ j.1572-0241.2004.04050.x. Nagashima N, Watanabe T, Nakamura M, Shalabi A, Burdick JF. Decreased effect of immunosuppression on immunocompetence in African–Americans after kidney and liver transplantation. Clin Transplant. 2001;15:111–115. doi:10.1034/j.1399-0012.2001. 150207.x. Dirks NL, Huth B, Yates CR, Meibohm B. Pharmacokinetics of immunosuppressants: a perspective on ethnic differences. Int J Clin Pharmacol Ther. 2004;42:701–718.
Dig Dis Sci (2010) 55:883–889 39. Pescovitz MD, Guasch A, Gaston R, et al. Equivalent pharmacokinetics of mycophenolate mofetil in African-American and Caucasian male and female stable renal allograft recipients. Am J Transplant. 2003;3:1581–1586. doi:10.1046/j.1600-6135.2003. 00243.x. 40. Chen ML. Ethnic or racial differences revisited: impact of dosage regimen and dosage form on pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2006;45:957–964. doi:10.2165/ 00003088-200645100-00001. 41. Maggard M, Goss J, Ramdev S, Swenson K, Busuttil RW. Incidence of acute rejection in African–American liver transplant recipients. Transplant Proc. 1998;30:1492–1494. doi:10.1016/ S0041-1345(98)00330-3. 42. Gaynor JJ, Moon JI, Kato T, et al. A cause-specific hazard rate analysis of prognostic factors among 877 adults who received primary orthotopic liver transplantation. Transplantation. 2007; 84:155–165. doi:10.1097/01.tp.0000269090.90068.0f. 43. Navarro V, Herrine S, Katopes C, Colombe B, Spain CV. The effect of HLA class I (A and B) and class II (DR) compatibility on liver transplantation outcomes: an analysis of the OPTN database. Liver Transpl. 2006;12:652–658. doi:10.1002/lt.20680.
889 44. Neumann UP, Langrehr JM, Lang M, et al. Impact of HLA matching upon outcome after liver transplantation. Transplant Proc. 2002;34:1499–1500. doi:10.1016/S0041-1345(02)02946-9. 45. Langrehr JM, Puhl G, Bahra M, et al. Influence of donor/recipient HLA-matching on outcome and recurrence of hepatitis C after liver transplantation. Liver Transpl. 2006;12:644–651. doi: 10.1002/lt.20648. 46. Tector AJ, Mangus RS, Chestovich P, et al. Use of extended criteria livers decreases wait time for liver transplantation without adversely impacting post transplant survival. Ann Surg. 2006;244:439–450. 47. Uemura T, Ikegami T, Sanchez EQ, et al. Late acute rejection after liver transplantation impacts patient survival. Clin Transplant. 2008;22(3):316–323. 48. Guadagnoli E, McNamara P, Evanisko MJ, Beasley C, Callender CO, Poretsky A. The influence of race on approaching families for organ donation and their decision to donate. Am J Public Health. 1999;89:244–247. doi:10.2105/AJPH.89.2.244. 49. Siminoff LA, Burant CJ, Ibrahim SA. Racial disparities in preferences and perceptions regarding organ donation. J Gen Intern Med. 2006;21:995–1000. doi:10.1007/BF02743151.
123
