Organ allocation in the United States is designed for the equitable distribution of a scare resource: deceased donor organs. Patients are prioritized to receive organs for liver transplantation (LT) according to their Model for End-Stage Liver Disease (MELD) score, an objective assessment of their risk of dying on the wait list.1, 2 Hence, 2 candidates with similar MELD scores should have an equal chance of receiving a transplant, regardless of race, gender, geography, or economics. However, there are multiple patient-specific and health care–specific barriers to LT that potentially compromise this equitable allocation system (Fig. 1).
The path to LT begins with recognition of chronic liver disease. The burden of chronic liver disease in the United States is underestimated, and not all persons who have underlying liver disease might be recognized in a timely manner.3 Populations at high risk for liver disease, such as certain minority subgroups (eg, Asian immigrants) and intravenous drug users, may have inadequate access to care, and this will further delay recognition of their underlying disease.4 A lack of recognition of nonalcoholic fatty liver disease (NAFLD) may also play a role. Moreover, the first interaction with a health care professional may dictate the path taken by a person with chronic liver disease; interactions in an academic setting versus a community hospital or with a specialist versus a generalist may lead to different levels of care.
When chronic liver disease is appropriately identified, recognition of the need for a transplantation evaluation may be variable. Once again, specialty care, an academic setting, or easy access to a transplant center may favor timely referral and appropriate listing. Unfortunately, the evaluation process for LT and registration on the waiting list may not be uniform. Certain groups such as women, non-Caucasians, older persons, and those with noncommercial insurance or certain diagnoses [eg, alcoholic liver disease (ALD)] may be disadvantaged.5, 6 Furthermore, rates of registration on the waiting list are lower for rural/small-town residents.7
Even after registration on the waiting list, disparities exist in access to LT; these are driven mostly by organ availability and geography. Organ availability differs by region, and even within a region, the likelihood of LT varies among donor service areas (DSAs).8-10 Local organ availability and center-specific transplant practices may also play a role. For example, centers vary by volume, with high-volume centers having shorter waiting times and performing more LT procedures for patients with lower MELD scores.11 Women, obese persons, and certain racial/ethnic groups have lower rates of transplantation.12-14 Finally, donor factors such as age, steatosis, organ size, and donor-recipient matching often lead to reshuffling of the order of recipients for LT.15, 16 Hence, the receipt of LT is the culmination of a complex process in which potential candidates for transplantation may inequitably be left behind at each step of the way.
Ethnic and racial disparities are evident at almost all steps along this continuum. Sociodemographic barriers may explain part of the disparity early in the process (disease recognition, transplant evaluation, and wait-list registration); however, their overarching influence on access to LT is less clear. In this issue of Liver Transplantation, Mathur et al.17 examine the effect of geography as a potential confounder of race and access to LT. The authors conducted a Scientific Registry of Transplant Recipients analysis of data submitted to the Organ Procurement and Transplantation Network (OPTN). They considered all adult candidates with chronic end-stage liver disease on the wait list between 2002 and 2007 and included persons listed with a diagnosis of hepatocellular carcinoma. The primary variable of interest was candidate race, and the primary outcome of interest was receipt of LT. Candidates were followed until LT, death, the granting of a MELD exception score, or the end of the observation period (whichever came first). Separate multivariable Cox models were created with adjustments for the consolidated OPTN region, individual OPTN region, and DSA (the primary level of organ distribution). Rates of LT across races were compared after stratification by DSA. Stratification allowed them to examine the effect of race within a DSA by the assignation of a baseline hazard unique to each DSA. Finally, effect modification of the association between candidate race and receipt of LT by MELD and geography was considered.
Of the 39,114 candidates, 74.1% were Caucasian, 13.9% were Hispanic, 7.3% were African American, and 3% were Asian. African Americans were more frequently listed for hepatitis C, had higher MELD scores at listing, and were more likely to require dialysis. Hispanics tended to have a higher prevalence of diabetes and blood type O and to have a higher body mass index with respect to other candidate races. Before the adjustment by DSA, African American candidates had a 10% decreased chance of receipt of LT in comparison with Caucasians. After the adjustment by DSA, this decreased to 2% and was no longer significant. Therefore, variability at the DSA level was a confounder for the association between African American candidate race and receipt of LT.
In contrast, Hispanics had an 8% lower rate of LT versus Caucasians (hazard ratio = 0.92, P = 0.011) even after the adjustment for DSA. With stratification by DSA, this difference in the receipt of LT was pronounced at MELD scores < 20 (a 15% lower transplant rate), but the difference was no longer present at higher MELD scores. With respect to Asians, there was no significant difference in LT rates versus Caucasians. An analysis of MELD subgroups, however, showed that Asian candidates with lower MELD scores6-14 had a 24% higher transplant rate versus Caucasians, but a lower transplant rate (15%-46%) was observed at MELD scores > 15. Moreover, AAs and Asians had 37% and 27% lower mortality rates on the wait list in comparison with Caucasians, whereas rates between Hispanics and Caucasians were similar.
Therefore, at least for African American candidates, the effect of candidate race on access to LT was mostly abrogated by the consideration of DSA. This suggests that African American candidates are likely overrepresented in DSAs with organ shortages. Therefore, with respect to racial disparities between African Americans and Caucasians and receipt of transplantation, location matters.
The persistently lower rates of transplantation for Hispanics even after consideration of DSAs are a concern. It is likely that unmeasured factors still make geography responsible for this ethnic disparity. Hispanic candidates may be overrepresented at centers that perform transplantation for candidates with higher MELD scores. Therefore, the consideration of the LT center may attenuate the effect of Hispanic ethnicity on access to LT. Ahmad et al.11 recently observed that a higher percentage of Hispanic candidates (13.8% versus 11.5%) were listed at medium-volume centers (50-99 annual transplants) versus high-volume centers (>100 transplants annually). Medium-volume centers perform transplantation for fewer persons with MELD scores less than 18 (19.7% versus 27.8%) and have a longer mean waiting time (357 versus 256 days). Furthermore, Volk et al.14 recently analyzed the same United Network for Organ Sharing database (2003-2008) used by the present study and observed that Hispanics are overrepresented in DSAs with longer median waiting times for LT. After stratification by DSA, disparities in LT between Hispanics and Caucasians disappeared. Technical considerations such as adjustments for exception status and the removal of inactive patients may be responsible for some of the incongruence between the studies.
Other reasons for lower transplantation rates among Hispanics may play a role. The prevalence of comorbidities such as obesity and diabetes and the higher rate of blood type O may lead to extensive donor-recipient matching at the time of transplantation, which would further limit the rate of LT in Hispanics with lower MELD scores. On the other hand, it is possible that Caucasians (the reference group) have etiologies of liver disease that allow transplantation at lower MELD scores. For example, twice the number of Caucasians underwent transplantation for cholestatic disease in comparison with Hispanics (9.8% versus 5.5%), and because the analysis was censored at the receipt of a MELD exception score, disparity by etiology may be partially responsible.
With respect to the lower transplant rates in Asians with MELD scores >15, a combination of a center effect and donor issues such as body size may be partially responsible. However, the overall rates of transplantation were similar between Caucasians and Asians.
The study by Mathur and colleagues17 is important for several reasons. It caps a triad of investigations that have substantially explained away a purported disparity in access to LT by race.12, 14 This has been done by careful analysis and stratification by DSA; this approach should be considered in future analyses of events on the waiting list. It therefore lays the foundation for further investigation into whether the extensive list of potential barriers to LT (Fig. 1) can be deconstructed into a smaller core that can actually be amended to improve the organ allocation system. Whether an even smaller geographic unit (ie, the transplant center) plays a role in explaining some of the disparities not explained by region or DSA remains to be seen.
More importantly, regardless of whether disparities in access to LT occur at the regional level, DSA level, or center level, the pervading influence of geography on the organ allocation system, as demonstrated by Mathur and colleagues,17 is a concern. Geographic incongruence serves to undermine an organ allocation scheme based on equity and needs to be addressed to make the convoluted and complex path to LT less cumbersome for persons with chronic liver disease, regardless of race, gender, payer, or any other status.