Health disparity is defined as a significant inconsistency in the overall rate of disease, measured by incidence, prevalence, morbidity, mortality, and survival in a specific population, when compared with those same factors in the health status of the general population.1 In the 1980s, the Department of Health and Human Services and the American Cancer Society reported health discrepancies for several malignancies in poor and minority populations, notably among blacks when compared with whites. Lack of health insurance, inability to access medical care, poverty, and low education level were suggested to be possible causes of the discrepancies.2,3 In addition, low socioeconomic status may lead to lower rates of cancer screening and delay in diagnosis, causing higher mortality rates.4–6 Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer mortality and the third most common cause of cancer-related deaths worldwide.7,8 Despite recent advances in screening and treatment for HCC, racial disparities in incidence and mortality persist. Liver transplantation, hepatic resection, and early-stage radiofrequency ablation are considered to be potentially curative treatment modalities for early HCC (single nodule of <5 cm or up to 3 nodules of ≤3 cm with no nodal or vascular invasion).9 Of these treatment modalities, liver transplantation is the most effective. In a recent study of localized-stage cases that received curative therapy, when compared with whites, blacks had a higher mortality rate, whereas Asians and Pacific Islanders had a lower one.10 We sought to examine the association between race and mortality among U.S. adults with HCC who underwent liver transplantation.
The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with HCC who underwent liver transplantation from 2004 to 2009, using International Classification of Disease for Oncology codes (ICD-O-3; 8170–8175). We included a homogeneous cohort of patients with early HCC, as defined in the prior paragraph. Patients with fibrolamellar carcinoma (ICD-O-3, 8171) and those diagnosed within 1 month before death were excluded. All-cause mortality and cause-specific mortality were calculated for subgroups based on race/ethnicity (white, black, or Asian/Pacific Islander). Time-to-event data were summarized with a Kaplan-Meier survival analysis and compared by use of log rank tests. The causes of death were described by racial subgroup and compared by use of a χ2 test. Multivariate Cox proportional hazard and subdistribution hazard regression models were used to quantify the effect of race on all-cause and cause-specific mortality. Covariates analyzed in all regression models included: race, age, sex, SEER histologic stage, marital status, tumor size, histologic grade, and lymph or vascular invasion. Statistical analysis was performed with SEER*Stat software 8.0.1 and SPSS 20.0.
During the study period, 2632 patients (74.5% males) met our inclusion criteria. Among the included patients who underwent liver transplantation, 1989 were white (75.9%), 223 black (8.4%), and 409 Asian/Pacific Islander (15.5%). The median survival was 115 (95% CI, 103–128), 85 (95% CI, 62–107), and 121 (95% CI, 110–138) months, for whites, blacks, and Asians/Pacific Islanders, respectively (log rank test; P = .02; Figure 1). Asians/Pacific Islanders were more likely to die of graft failure or liver disease (13.4%) than were whites (8.0%) or blacks (8.5%; P < .01; Table 1). Blacks were more likely to die of an infection (9.0%) than were whites (6.1%) or Asians/Pacific Islanders (3.2%; P < .01). In the multivariate analysis; black recipients had higher all-cause mortality than did whites and Asians/Pacific Islanders (adjusted hazard ratio [aHR], 1.67; 95% CI, 1.02–2.72). Paradoxically, black recipients had lower liver-related mortality (aHR, 0.02; 95% CI, 0.01–0.31) than did whites (aHR, 0.10; 95% CI, 0.59–0.95) and Asians/Pacific Islanders.
Figure 1.
Kaplan-Meier Survival Analysis; A/PIs (Asian and Pacific Islanders)
Table 1.
Deaths by cause and race/ethnicity
| Cause of death, n (%) | White (n = 1989) | Black (n = 223) | Asian/Pacific Islander (n = 409) |
|---|---|---|---|
| Liver-related or graft failure* | 161 (8.0) | 19 (8.5) | 50 (13.4) |
| Infection* | 122 (6.1) | 20 (9.0) | 12 (3.2) |
| Other malignant cancer | 25 (1.2) | 1 (0.4) | 8 (2.1) |
| Cerebrovascular | 10 (0.5) | 1 (0.4) | 2 (0.5) |
| Cardiovascular | 20 (1.0) | 1 (0.4) | 4 (1.1) |
| Renal failure | 12 (0.6) | 2 (0.9) | 1 (0.3) |
χ2 test for comparison between racial subgroups, P < 0.01.
Our results show persistent racial disparities in patients with HCC, even after receipt of a liver transplant. Blacks were more likely to die of causes potentially associated with overimmunosuppression (infection and septicemia), whereas Asians/Pacific Islanders were more likely to die of causes associated with underimmunosuppression (graft failure and liver disease). Black liver transplant recipients have persistently higher overall mortality, perhaps because of a higher rate of infection associated with overimmunosuppression. Asians/Pacific Islanders with HCC have better overall survival after liver transplantation than do the other races, despite a high rate of graft failure or liver-related mortality. Additional research to identify possible causes of these disparities, such as biological factors (eg, donor-recipient mismatches and HLA antigen status), the need for higher or lower levels of immunosuppression, differences in drug absorption, and systemic complications of therapy, are warranted.
Acknowledgments
Research grant from Yale Liver Center-Clinical and Translation Core, NIDDK/P30-34989 (J.K.L).
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