Author Information1
Gandhi, Mallika2, Gupte, Sahil3, Valluri, Medha4
(Editor: Koizumi, Naoru5)
1 All authors are listed in Alphabetical Order.
2 Dominion High School, VA, 3 Monroe Township High school, NJ, 4 Thomas Jefferson High School for Science and Technology, VA, 5 George Mason University
Background
Prior literature reports the impact of opioid pandemic on organ transplants. Durand (2018), for instance, compared outcomes transplants that used organs from donors that died of overdoses and organs from more traditional deaths varied in organ transplants. The data analyzed over 138,000 deceased donors and over 337,000 solid organ transplant recipients, and found a substantial rise in organ transplants from overdose death donors (ODD). The study found that outcomes for recipients of ODD organs were comparable or even better than those for organs from traditional deceased donors and medically suitable deceased donors. (Durand, 2018). Also in 2018, a study based on kidney donors during the opioid crisis, specifically among hepatitis C virus (HCV)-infected donors, was published in the American Journal of Nephrology. Data showed that from 2010 to 2016 there was a 26% increase in overall kidney donors, as well as a 277% increase in donors who died from drug overdoses, 19% of whom had HCV. These overdose and HCV-infected donors were generally younger and healthier, with better kidney donor profile index (KDPI) scores, however their kidneys were not used as much compared to non-HCV-infected donors (Chute & Sise, 2018).
In 2020, during the COVID 19 pandemic, the escalation of the rate of drug overdose mortality was greater than any increase between 1999 and 2019 (Friedman & Hansen, 2022). Two years later, in 2022, Friedman and Hansen evaluated the trend in drug overdose mortality throughout the United States, and found that overdose death rates increased across all racial and ethnic groups. However, some groups were more affected than others, such as the death rates of black people increased from 24.7 to 36.8 from just 2019 to 2020, which was 16.3% higher than that for white individuals in 2020. In the same year, the total number of liver and kidney transplants experienced a 16% drop (Nimmo et al., 2022). Perego et al. confirmed this by demonstrating that the number of global kidney transplants during the pandemic which had plummeted, presumably caused by the lessened focus on non-COVID related healthcare activities during the first wave, and kidney transplant centers had temporarily stopped their work due to the high risk of COVID-19. (Perego et al., 2022). It is, however, unknown whether the increase in overdose deaths contributed to the absolute number and share of ODD transplants during the same period.
Objective
Our study intends to investigate how liver donor and transplant recipient characteristics change pre- and post-pandemic. While also comparing transplant outcomes that used donor livers from different causes of death pre- and post-pandemic, such as drug overdose, stroke, blunt injury, cardiovascular disease, natural death, and more.
Methods
A descriptive statistical analysis was performed to compare liver transplant recipients and their donor characteristics pre- (2018 – 2019) and post- (2020-2022) pandemic periods. The first statistical analysis was a t-test (t=spn11+n21X1ˉ-1X1ˉ−X2ˉ), which was used to compare the donor characteristics pre and post-pandemic and how different they are from each other. The next statistical analysis was a chi squared test (χ2=∑Ei(Oi−Ei)2), which was used to tell if there was a substantial association between donor characteristics pre and post-pandemic. A Cox regression analysis was done on significant variables (p<0.05) and how it had impacted patient mortality and graft failure. Pre- and post-pandemic data were compared to examine how the significant variables changed.
Results:
There was a statistically significant difference in the number of male patients pre- (8,404 (66.21%)) and post-pandemic (10,796 (64.42%)) (p=0.001). There was a significant difference in the average age of the patients pre- (55.63 (11.30)) and post-pandemic (54.66(11.66)) (p<0.001). The proportion of Hispanic patients was higher post than pre-pandemic (p=0.029). The wait time was higher pre-pandemic (p<0.001). The proportion of male donors was higher post-pandemic (p<0.001). The proportion of donors that died of drug overdose was higher post-pandemic (p<0.001). The proportion of donors that died of stroke was higher post-pandemic (p<0.001). The proportion of donors that died of blunt force was higher post-pandemic (p=0.045). The proportion of donors that have a history of hypertension was higher post-pandemic (p=0.019). The proportion of donors that have suffered circulatory death was higher post-pandemic (p<0.001). The proportion of donors that have a pre-existing condition was higher post-pandemic (p=0.006). The proportion of local and national liver donation was higher pre-pandemic (p<0.001).
Figure 1: Descriptive statistical analysis table comparing different variables of liver donation pre-pandemic and post-pandemic.
| Characteristics | Pre-pandemic (n = 34) | Post-pandemic (n = 34) | p-value |
| Patient Characteristics | |||
| Male, n (%) | 8,404 (66.21%) | 10,796 (64.42%) | 0.001 |
| Age, mean (sd) | 55.63 (11.30) | 54.66 (11.67) | <0.001 |
| White | 9,057 (71.36%) | 11,908 (71.06%) | 0.572 |
| Black | 918 (7.23%) | 1,132 (6.75%) | 0.11 |
| Hispanic | 1,978 (15.58%) | 2,770 (16.53%) | 0.029 |
| Asian | 518 (4.08%) | 665 (3.97%) | 0.625 |
| Other | 221 (1.74%) | 283 (1.69%) | 0.731 |
| Wait time (in days), median (IQR) | 83 (451.84) | 35 (396.04) | <0.001 |
| Retransplant, n (%) | 459 (3.62%) | 634 (3.78%) | 0.453 |
| BMI at the time of TX, mean (sd) | 29.47 (5.88) | 29.49 (6.12) | 0.602 |
| Donor Characteristics | |||
| Male, n (%) | 7,606 (59.93%) | 10,394 (62.02%) | <0.001 |
| Age, mean (sd) | 43.49 (15.24) | 43.16 (14.84) | 0.105 |
| White | 8,156 (64.26%) | 10,677 (63.71%) | 0.332 |
| African American | 2,310 (18.20%) | 3,112 (18.57%) | 0.417 |
| Hispanic | 1,751 (13.80%) | 2,317 (13.83%) | 0.941 |
| Asian | 327 (2.58%) | 444 (2.65%) | 0.697 |
| Other | 221 (1.74%) | 283 (1.69%) | 0.731 |
| Drug overdose | 1,991 (15.69%) | 3,290 (19.63%) | <0.001 |
| Stroke | 3,753 (29.57%) | 4,631 (27.63%) | <0.001 |
| Blunt Injury | 2,166 (17.07%) | 2,713 (16.19%) | 0.045 |
| Cardiovascular disease | 2,417 (19.04%) | 3,131 (18.68%) | 0.434 |
| Natural death | 435 (3.43%) | 527 (3.14%) | 0.177 |
| Other | 1,930 (15.21%) | 2,466 (14.72%) | 0.242 |
| Creatinine at the time of TX, mean (sd) | 1.90 (2.00) | 1.90 (2.02) | 0.058 |
| Diabetes at the time of TX, n (%) | 1,770 (14.08%) | 2,244 (13.60%) | 0.239 |
| Hypertensive at the time of TX, n (%) | 4,885 (38.95%) | 6,200 (37.60%) | 0.019 |
| BMI at the time of TX, mean (sd) | 28.62 (6.79) | 28.56 (6.66) | 0.931 |
| Donor after Circulatory Death, n (%) | 1,079 (8.50%) | 1,825 (10.89%) | <0.001 |
| Expanded Criteria Donor, n (%) | 3,368 (26.54%) | 4,209 (25.12%) | 0.006 |
| Transplant Characteristics | |||
| HLA mismatch level, mean (sd) | 4.66 (1.09) | 4.65 (1.06) | 0.573 |
| Locally shared, n (%) | 8,288 (65.30%) | 6,230 (37.18%) | <0.001 |
| Regionally shared, n (%) | 3,744 (29.50%) | 5,021 (29.96%) | 0.39 |
| Nationally shared, n (%) | 660 (5.20%) | 5,507 (32.86%) | <0.001 |
There was no significant difference in the survival time of a patient after receiving a transplant from an ODD donor before or after the pandemic (p>0.05). Furthermore, the regressions in Figure 1 show similar survival times throughout all causes of death before and after the pandemic.
Figure 2. Patient survival time by cause of death of the organ donor before (left) vs. after (right) the COVID-19 pandemic
There was no significant difference in the survival of a graft before and after the COVID-19 pandemic. In Figure 2, it is illustrated that the livers that came from donors who died of an ODD showed a similar graft survival to organs donated patients with traditional causes of death.
Figure 3. Graft survival time by cause of death of the organ donor before (left) vs. after (right) the COVID-19 pandemic
The Cox regression models showed that the statistically significant variables of patient mortality and graft failure were recipient age, local liver transplant, regional liver transplant, and retransplant. Older recipient age had increased patient mortality by 2.3% pre-pandemic (p<0.001) and 3.9% post-pandemic (p<0.001), and older recipient age increased graft failure by 1.1% pre-pandemic (p=0.003) and 2.8% post-pandemic (p<0.001). Locally donated livers had reduced patient mortality by 42.2% pre-pandemic (p=0.013) and 33.16% post-pandemic (p=0.001), and locally donated livers reduced graft failure by 42.5% pre-pandemic (p=0.001) and 3.4% post-pandemic (p<0.001). Regionally donated livers had reduced patient mortality 37.74% pre-pandemic (p=0.013) and 39.05% post-pandemic (p<0.001), and regionally donated livers reduced graft failure by 39.03% pre-pandemic (p=0.006) and 0.27% post-pandemic. Getting a liver retransplant increased patient mortality by 109.5% pre-pandemic and 209.6% post-pandemic (p<0.001), and getting a liver retransplant increased graft failure by 97.9% pre-pandemic and 201.0% post-pandemic (p<0.001).
Figure 4. Cox-regression model of how different variables impacted patient mortality before COVID-19 (top) and after COVID-19 (bottom).
| Variable | HR | P-Value | [95% | C.I.] |
| Recipient Factors | ||||
| Recipient Age (yrs) | 1.024 | <0.001 | 1.016 | 1.032 |
| Transplant Factors | ||||
| local | 0.5798 | 0.013 | 0.4079 | 0.8242 |
| regional | 0.6226 | 0.013 | 0.4289 | 0.9036 |
| retx | 2.095 | <0.001 | 1.5 | 2.926 |
| Variable | HR | P-Value | [95% | C.I.] |
| Recipient Factors | ||||
| Recipient Age (yrs) | 1.039 | <0.001 | 1.029 | 1.05 |
| Transplant Factors | ||||
| local | 0.6684 | 0.001 | 0.5216 | 0.8564 |
| regional | 0.6095 | <0.001 | 0.4687 | 0.7927 |
| retx | 3.096 | <0.001 | 2.187 | 4.382 |
Figure 5. Cox-regression model of how different variables impacted graft failure before COVID-19 (top) and after COVID-19 (bottom).
| Variable | HR | P-Value | [95% | C.I.] |
| Recipient Factors | ||||
| Recipient Age (yrs) | 1.011 | 0.003 | 1.004 | 1.018 |
| Transplant Factors | ||||
| local | 0.5749 | 0.001 | 0.4134 | 0.7995 |
| regional | 0.6097 | 0.006 | 0.4297 | 0.865 |
| retx | 1.979 | <0.001 | 1.443 | 2.714 |
| Variable | HR | P-Value | [95% | C.I.] |
| Recipient Factors | ||||
| Recipient Age (yrs) | 1.028 | <0.001 | 1.018 | 1.037 |
| Transplant Factors | ||||
| local | 0.6557 | <0.001 | 0.5249 | 0.819 |
| regional | 0.9973 | 0.951 | 0.9151 | 1.087 |
| retx | 3.010 | <0.001 | 2.19 | 4.137 |
Conclusion
Ultimately, there was no significant difference in the survival time of the patient and the graft when the organ came from a donor who died of an ODD. However, there was a visible difference in the survival of a patient and graft before and after the Covid-19 pandemic.
References:
1. Chute, Donald F., and Meghan E. Sise. “Effect of the Opioid Crisis on the Donor Pool for Kidney Transplantation: An Analysis of National Kidney Deceased Donor Trends from 2010–2016.” American Journal of Nephrology, vol. 47, no. 2, Feb. 2018, pp. 84–93. Silverchair, https://doi.org/10.1159/000486516.
2. Durand, C. M., Bowring, M. G., Thomas, A. G., Kucirka, L. M., Massie, A. B., Cameron, A., Desai, N. M., Sulkowski, M., & Segev, D. L. (2018). The drug overdose epidemic and deceased-donor transplantation in the united states. Annals of Internal Medicine, 168(10), 702. https://doi.org/10.7326/m17-2451
3. Friedman, J. R., & Hansen, H. (2022). Evaluation of increases in drug overdose mortality rates in the US by race and ethnicity before and during the covid-19 pandemic. JAMA Psychiatry, 79(4), 379. https://doi.org/10.1001/jamapsychiatry.2022.0004
4. Perego, M., Samuele Iesari, Maria Teresa Gandolfo, Alfieri, C., Delbue, S., Cacciola, R.,
5. Ferraresso, M., & Evaldo Favi. (2022). Outcomes of Patients Receiving a Kidney Transplant or Remaining on the Transplant Waiting List at the Epicentre of the COVID-19 Pandemic in Europe: An Observational Comparative Study. Pathogens, 11(10), 1144–1144. https://doi.org/10.3390/pathogens11101144
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7. Nimmo, A., Gardiner, D., Ushiro-Lumb, I., Ravanan, R., & Forsythe, J. L. R. (2022). The global impact of covid-19 on solid organ transplantation: Two years into a pandemic. Transplantation, 106(7), 1312-1329. https://doi.org/10.1097/tp.0000000000004151