Author Information1
Jung, Claire2; Raja, Harshita3; Weber, William4
(Editor: Li, Meng-Hao5)
1 All authors are listed in alphabetical order
2 Flintridge Preparatory School, CA, 3Tesla STEM High School, WA, 4Xavier High School, CT, 5George Mason University, VA
Background
Transplantation is a surgical process of removing healthy organs from a donor into an ill recipient. This process is broken up into many steps and initially begins with a medical evaluation where both the donor and recipient undergo extensive tests to reduce risk and further complications in the future. Once an evaluation is complete, it is obligatory to find the most appropriate match with others who share common blood type, tissue type, and the size of the organ being transplanted. Next, the surgery is performed. The duration of surgery can vary depending on the type of organ being transplanted: in the case of a liver transplant it can take as long as 12 hours, in the case of an intestinal transplant it can take as long as 8 hours, and in the case of a multivesicular transplant such as the transplantation of the liver and intestine simultaneously it can take more than 12 hours. Following the procedure, the recipient must be properly medicated for their entire life and undergo regular medical visits to monitor organ function and overall health. The purpose of transplantation is to improve the quality of life and the survival rate for recipients with end-stage organ failure.
Two well-known types of transplantations are liver transplants and intestinal transplants. As a point of fact, such things are multivesicular transplants can be done, where these organs are transplanted simultaneously. However, such a procedure is not common. According to a new policy enacted in 2002, those in need of liver transplants are placed on a scaled system which prioritizes patients based on the severity of the disease known as MELD score, while waiting for a transplant rather than waiting time alone. It has reduced pre-transplant mortality without increasing post-transplant deaths, despite transplanting sicker patients. The policy change is known to have significantly decreased the waitlisted patients, demonstrating a decline that has not been seen in a decade. As a result, the age of liver recipients has risen, from 1% in 1997 to 51% in 2004 being over 50 years old (Freeman et al. 2008). Contrarily, intestinal transplants are much rarer and more difficult to do. Since 1997, survival rates following intestinal transplantation have shown consistent improvement (Freeman et al. 2008). By 2005, the 1-year adjusted graft survival increased from 52% ± 6.3% to 75% ± 3.4%, and 1-year adjusted patient survival improved from 57% ± 6.5% to 80% ± 3.3%. For recipients of intestine alone transplants, unadjusted patient survival rates were 81% at 1 year, 67% at 3 years, 54% at 5 years, and 43% at 10 years (Shiffman et al. 2004). These improvements can be attributed to induction agents being used at the beginning of the surgeries. Candidates for intestinal transplants usually have irreversible intestinal failure and complications from parenteral nutrition, such as loss of venous access, severe catheter infections, or liver disease.
Many studies have manifested the racial disparities associated with several types of transplantations. Specifically, a study of 6,585 simultaneous pancreas-kidney transplants, a longer-term study showed that African Americans were at a 38% – 47% higher risk of pancreas graft failure and late death-censored kidney failure compared to non-African Americans because of immunologic graft loss and rejection. Additionally, transplantations performed in Hispanics and Asians tend to result in the best outcomes and graft survival rates. Even in studies where reports demonstrate results superior to national data, there is a significant difference in success rates between the races. Over 15 years, there is a 17% increased risk of death, 27% increased risk of kidney graft loss, and 15% increased risk of pancreas graft loss in African American patients compared to Caucasian patients.
Objective
The study looks at racial disparities in intestine alone and intestine-liver transplants in the United States. This will be done through comparative studies and statistical analysis between different race groups and transplant success rates.
Methods
Using the UNOS database between June 15, 2024 and July 12, 2024, data was extracted from the years of 2000 to 2022. Specifically, data about intestine-alone and liver-intestine transplants were taken from the database. Basic characteristics about the donor, patient and transplant were compared by basic demographics such as age, sex and ethnicity, and transplant organ source (local, regional, national) . For the intestine-alone transplantation test group, survival curves and the estimates for transplant outcomes by 5 race categories (White, Black, Hispanic, Asian, or Other) were obtained using the Kaplan-Meier graph analysis. For the simultaneous liver-intestine transplantation test group, the race categories white and non-white were used due to a small test sample with few cases of both white and non-white, with 17 tested participants in total. Using p-values, chi-squared tests and hazardous rates as a result of COX regressions, significance on graft and patient survival was tested. The end analysis was based on graft survival and patient mortality. Any missing or erroneous data points were removed from being tested. Log-rank tests were used to test the equality of the curves. All the analyses were done in R programming and the statistical significance was defined by p<0.05.
Results
Descriptive Analysis
Table 1: Descriptive Analysis
| Characteristics | Intestine-alone TX(n = 387) | Liver-intestinal TX(n = 17) | p-value |
| Patient Characteristics | |||
| Male, n (%) | 181 (46.77%) | 10 (58.82%) | 0.33 |
| Age, mean (sd) | 42.4 (12.77) | 35.71 (15.30) | 0.042 |
| Race, n (%) | |||
| White | 304 (78.55%) | 11 (64.71%) | 0.227 |
| Black | 42 (10.85%) | 2 (11.76%) | 0.71 |
| Hispanic | 31 (8.01%) | 3 (17.65%) | 0.164 |
| Asian | 7 (1.81%) | 1 (5.88%) | 0.293 |
| Other | 3 (0.78%) | 0 (0.00%) | >0.999 |
| Retransplant Status, n (%) | 31 (8.01%) | 1 (5.88%) | >0.999 |
| Wait time (in days), median (IQR) | 44 (147.40) | 166 (393.80) | <0.001 |
| BMI at the time of TX, mean (sd) | 23.27 (4.30) | 22.96 (2.91) | 0.927 |
| Donor Characteristics | |||
| Male, n (%) | 236 (60.98%) | 6 (35.29%) | 0.034 |
| Age, mean (sd) | 28.08 (9.87) | 29.29 (8.12) | 0.285 |
| Race, n (%) | |||
| White | 244 (63.05%) | 8 (47.06%) | 0.183 |
| African American | 76 (19.64% | 3 (17.65%) | >0.999 |
| Hispanic | 54 (13.95%) | 5 (29.41%) | 0.09 |
| Asian | 10 (2.58%) | 0 (0.00%) | >0.999 |
| Other | 3 (0.78%) | 0 (0.00%) | >0.999 |
| Diabetes at the time of TX, n (%) | 21 (5.43%) | 1 (5.88%) | >0.999 |
| Hypertensive at the time of TX, n (%) | 32 (8.67%) | 2 (11.76%) | 0.654 |
| BMI at the time of TX, mean (sd) | 22 (3.67) | 24.7 (4.85) | 0.10 |
| Donor after Cardiac Death, n (%) | 0 (0.00%) | 0 (0.00%) | na |
| Expanded Criteria Donor, n (%) | 2 (0.54%) | 0 (0.00%) | >0.999 |
| Transplant Characteristics | |||
| HLA mismatch level, mean (sd) | 4.42 (1.23) | 4.92 (1.12) | 0.127 |
| Locally shared, n (%) | 85 (21.96%) | 10 (58.82%) | <0.001 |
| Regionally shared, n (%) | 55 (14.21%) | 2 (11.76%) | >0.999 |
| Nationally shared, n (%) | 247 (63.82%) | 5 (29.41%) | <0.001 |
There are 5 significant differences in logistics and demographics between simultaneous liver-intestine transplants and intestine alone transplants, all due to the p-values being less than 0.05. The average age of recipients for intestine-alone transplants is significantly higher than simultaneous transplants, shown by the p-value being 0.042. Additionally, the wait time for simultaneous liver-intestine transplants have a higher wait time than intestine alone transplants, with a p-value less than 0.001. With a p-value at 0.034, the proportion of male donors is higher for intestine alone transplants. The final two significant differences are regarding organ sourcing. A higher proportion of liver-intestinal transplants are locally sourced and shared (p < 0.001) and a higher proportion of intestine alone transplants are nationally sourced and shared (p < 0.001).
Kaplein Meyer Curves
Figure 1. Intestine-alone Transplants: Graft Survival by Patient Race
Figure 2. Liver-Intestinal Transplants: Graft Survival by Patient Race
Figure 3. Intestine-Alone Transplants: Patient Survival by Patient Race
Figure 4. Liver-Intestinal Transplants: Patient Survival by Patient Race
P-values showed 0.1 for intestine-alone graft survival by patient race, 0.3 for intestine-alone patient survival by patient race, 0.5 for liver-intestinal graft survival by patient race, and 0.6 for liver-intestinal patient survival by patient race. All these values are >0.05, so there were no significant p-values for the white, black, hispanic, or other test groups for both intestine transplants and simultaneous liver-intestine transplants. Although the Kaplan-Meier graph curves appear to have significant differences in the survival estimate over time, the rarity of these types of transplants resulted in very small sample sizes for liver-intestine transplants. Because of this, trends in survival rate based on race were not considered to be significant.
COX Regressions
We have removed the variable other_pt, which includes patients not included in Black, Hispanic, Asian, or White races because there are zero cases in simultaneous transplants and p-values were above 0.99.
Figure 5. Intestine Only Transplants: Graft Failure
| Characteristic | HR | 95% CI | p-value |
| Hispanic Donor | 1.58 | 1.113, 2.244 | 0.01 |
| Expanded Donor Including Brain Dead and DCD | 6.059 | 1.418, 25.88 | 0.015 |
| DONOR AGE (YRS) | 1.016 | 1.002, 1.029 | 0.02 |
| Male Recipient | 0.9527 | 0.7345, 1.236 | 0.715 |
| Black Recipient | 0.8638 | 0.5627, 1.326 | 0.503 |
| Hispanic Recipient | 1.179 | 0.7147, 1.947 | 0.518 |
| Asian Recipient | 0.3733 | 0.0925, 1.506 | 0.166 |
Figure 6. Intestine Only Transplants: Patient Mortality
| Characteristic | HR | 95% CI | p-value |
| Recipient Age | 1.026 | 1.014, 1.039 | <0.001 |
| Black Recipient | 1.228 | 0.7965, 1.894 | 0.352 |
| Hispanic Recipient | 1.388 | 0.7839, 2.459 | 0.261 |
| Asian Recipient | 0 | 0, Inf | 0.19 |
Figure 7. Liver-Intestinal Transplants: Graft Failure
| Characteristic | HR | 95% CI | p-value |
| Male Recipient | 0.8478 | 0.195, 3.685 | 0.826 |
| Black Recipient | 0.4018 | 0.0424, 3.805 | 0.427 |
| Hispanic Recipient | 1.22 | 0.2381, 6.252 | 0.811 |
| Asian Recipient | 0 | 0.000, Inf | 0.999 |
Figure 8. Liver-Intestinal Transplants: Patient Mortality
| Characteristic | HR | 95% CI | p-value |
| Male Recipient | 0.7005 | 0.1497, 3.278 | 0.651 |
| Black Recipient | 0.4202 | 0.0416, 4.245 | 0.462 |
| Hispanic Recipient | 1.458 | 0.2705, 7.853 | 0.661 |
| Asian Recipient | 0 | 0, Inf | >0.999 |
Out of our other tested variables, there was significance as seen from the COX regressions conducted. For intestine-alone transplants (graft failure), a hispanic donor increases graft failure by 58%, an expanded donor with Brain death and DCD increases graft failure by 500%, and higher donor age increases graft failure by 1.6%. For intestine-alone transplants (patient mortality), higher recipient age increases patient mortality by 2.6%. There were no significant variables in simultaneous liver-intestine transplants, probably due to its restricted sample size.
Conclusion
When examining the data we found that most p-values for race were greater than 0.05, this indicates that there was a failure to reject the null-hypothesis; meaning that there was a high probability of obtaining the observed results. With the intestine-alone and liver-intestinal transplants, all non-white ethnic groups seemed to have high graft survival estimates with the exception of Hispanic individuals. In addition, the significant values in other variables such as race of donor, patient age, and donor age signify that there is research needed to be performed to come to further conclusion. This gathers the probability of the transplant functioning at a finite time after transplantation, indicating a potential disparity in outcomes that warrants further investigation. There are some novel discoveries on intestine-only and simultaneous transplants, such as the significant disparity in donors, with a Hispanic donor resulting in increased graft failure.
References
1. Brown, Robert S., et al. “Liver and intestine transplantation.” American Journal of Transplantation 4 (2004): 81-92.
2. Freeman Jr, R. B., et al. “Liver and intestine transplantation in the United States, 1997–2006.” American Journal of Transplantation 8.4 (2008): 958-976.
3. Reese, Peter P., et al. “Racial disparities in preemptive waitlisting and deceased donor kidney transplantation: Ethics and solutions.” American Journal of Transplantation 21.3 (2021): 958-967.
4. Rogers, Jeffrey, et al. “Simultaneous pancreas‐kidney transplantation in Caucasian versus African American patients: Does recipient race influence outcomes?.” Clinical Transplantation 36.5 (2022): e14599.
5. Shiffman, Mitchell L., et al. “Liver and intestine transplantation in the United States, 1995–2004.” American Journal of Transplantation 6.5 (2006): 1170-1187.
6. Young, Carlton J., et al. “Redefining the influence of ethnicity on simultaneous kidney and pancreas transplantation outcomes: a 15-year single-center experience.” Annals of surgery 271.1 (2020): 177-183.