Abstract
This cohort study analyzes the impact of the Organ Procurement and Transplantation Network’s policy changes on mortality and post–liver transplant survival for pediatric patients on the waitlist.
Pediatric acute liver failure (PALF) is a highly morbid condition affecting previously healthy children. Liver transplant (LT) remains the only cure for PALF, representing 10% to 15% of pediatric LTs. Due to disparities that children face on the LT waitlist, the Organ Procurement and Transplantation Network (OPTN) has periodically amended its policies. We analyzed how policy changes impacted waitlist mortality and post-LT survival in PALF.
Methods
A cohort study was conducted using the Scientific Registry of Transplant Recipients (SRTR). Children with PALF (<18 years) placed on the LT waitlist between January 1989 and December 2020 were grouped based on Status 1/1A listing date and inclusion criteria (eFigure 2 in Supplement 2). Eras were constructed after review of OPTN liver-specific policies (eFigure 1 in Supplement 1). Waitlist mortality and post-LT patient and graft survival were evaluated as primary end points. Tests (Fisher, Kruskal-Wallis, survival, and Cox regression) were 2-sided, and P < .05 was considered significant. Statistical analysis was performed in fall 2023 in R version 4.2.2 (The R Foundation). This study was approved by the biomedical institutional review board at the University of Southern California, with a waiver of consent for secondary analyses of registry data.
Results
Waitlist
In total, 1495 pediatric patients were placed on the LT waitlist—443 (29.6%) in era 1, 649 (43.4%) in era 2, and 403 (27.0%) in era 3 (Table). The transplant rate increased from era 1 (71.8%) to era 3 (86.6%), while the proportion with waitlist deterioration or mortality decreased (19.2% and 7.2%, respectively). Era 3 had the lowest cumulative incidence of waitlist mortality (P < .001) (Figure, A).
Table. Patient Demographic Characteristics.
| Characteristica | No. (%) | P value | |||
|---|---|---|---|---|---|
| Overall | Era 1 | Era 2 | Era 3 | ||
| Waitlisted | |||||
| Patients | 1495 (100) | 443 (29.6) | 649 (43.4) | 403 (27.0) | NA |
| Age at listing, median (IQR), y | 6 (1-13) | 7 (2-13) | 6 (1-13) | 5 (1-12) | .48 |
| Sex | |||||
| Female | 678 (45.4) | 197 (44.5) | 295 (45.5) | 186 (46.2) | .89 |
| Male | 817 (54.6) | 246 (55.5) | 354 (54.5) | 217 (53.8) | |
| Race and ethnicityb | |||||
| Asian or Pacific Islander | 74 (4.9) | 15 (3.4) | 29 (4.5) | 30 (7.4) | <.001 |
| Black | 225 (15.1) | 71 (16.0) | 123 (19.0) | 61 (15.1) | |
| Hispanic | 416 (27.8) | 88 (19.9) | 205 (31.6) | 123 (30.5) | |
| White | 710 (47.5) | 261 (58.9) | 276 (42.5) | 173 (42.9) | |
| Otherc | 40 (2.7) | 8 (1.8) | 16 (2.5) | 16 (4.0) | |
| Removal cause | |||||
| Deteriorated or expired | 203 (13.6) | 85 (19.2) | 89 (13.7) | 29 (7.2) | <.001 |
| Improved | 79 (5.3) | 25 (5.6) | 33 (5.1) | 21 (5.2) | |
| Transplanted | 1185 (79.3) | 318 (71.8) | 518 (79.8) | 349 (86.6) | |
| Otherd | 28 (1.9) | 15 (3.4) | 9 (1.4) | 4 (1.0) | |
| Received transplant | |||||
| Patients | 858 (100) | 169 (19.7) | 371 (43.2) | 318 (36.9) | NA |
| Age at listing, median (IQR), y | 5 (1-11) | 5 (1-10) | 6 (1-11) | 5 (1-12) | .78 |
| Sex | |||||
| Female | 368 (42.9) | 77 (45.6) | 156 (42.0) | 135 (42.5) | .73 |
| Male | 490 (57.1) | 92 (54.4) | 215 (58.0) | 183 (57.5) | |
| Race and ethnicityb | |||||
| Asian or Pacific Islander | 42 (4.9) | 5 (3.0) | 14 (3.8) | 23 (7.2) | <.001 |
| Black | 137 (16) | 22 (13.0) | 63 (17) | 52 (16.4) | |
| Hispanic | 265 (30.9) | 32 (18.9) | 134 (36.1) | 99 (31.1) | |
| White | 393 (45.8) | 107 (63.3) | 150 (40.4) | 136 (42.8) | |
| Otherc | 21 (2.4) | 3 (1.8) | 10 (2.7) | 8 (2.5) | |
| Waiting time, median (IQR), d | 3 (2-6) | 4 (2-6) | 3 (2-6) | 3 (2-6) | .24 |
| Procedure type | |||||
| Split (deceased) | 244 (28.4) | 52 (30.8) | 120 (32.3) | 72 (22.6) | <.001 |
| Split (living donor) | 91 (10.6) | 21 (12.4) | 54 (14.6) | 16 (5.0) | |
| Whole liver | 523 (61.0) | 96 (56.8) | 197 (53.1) | 230 (72.3) | |
| Total cold ischemic time, median (IQR), h | 6.9 (5.1-8.8) | 8.3 (5.4-10.8) | 6.9 (5-8.7) | 6.5 (5.3-8.2) | <.001 |
| Time to graft failure, median (IQR), y | 3.4 (1.4-8.3) | 7.5 (2.3-12.1) | 3.1 (1.2-7.5) | 1.4 (0.5-3.2) | <.001 |
| Straight-line distance between donor and recipient hospitals, median (IQR), km | 371.7 (21.8-953.6) | 182.9 (16.5-643.0) | 345.0 (19.4-653.3) | 515.7 (108.6-1297.8) | <.001 |
| Donors | |||||
| Patients | 858 (100) | 169 (19.7) | 371 (43.2) | 318 (37.1) | NA |
| Age, median (IQR), y | 19 (5-32) | 21 (7-35) | 20 (10-33) | 14 (3-27) | <.001 |
| Sex | |||||
| Female | 358 (41.7) | 71 (42.0) | 158 (42.6) | 129 (40.6) | .87 |
| Male | 500 (58.3) | 98 (58.0) | 213 (57.4) | 189 (59.4) | |
| Race and ethnicityb | |||||
| Asian or Pacific Islander | 26 (3.0) | 2 (1.2) | 11 (3.0) | 13 (4.1) | <.001 |
| Black | 145 (16.9) | 22 (13) | 48 (12.9) | 68 (21.4) | |
| Hispanic | 181 (21.1) | 32 (18.9) | 101 (27.2) | 60 (18.9) | |
| White | 498 (58.0) | 107 (63.3) | 208 (56.1) | 172 (54.1) | |
| Otherc | 8 (0.9) | 3 (1.8) | 3 (0.8) | 5 (1.6) | |
| Height, median (IQR), cm | 160 (113-173) | 163 (116-178) | 165 (133-173) | 152 (99-170) | <.001 |
| Weight, median (IQR), kg | 58 (20-73) | 59 (20-75) | 61 (35-75) | 50 (17-69) | <.001 |
| Deceased | 767 (89.4) | 148 (87.6) | 317 (85.4) | 302 (95.0) | <.001 |
Abbreviation: NA, not applicable.
SI conversion factors: To convert kilometers to miles, divide by 1.6. To convert centimeters to inches, divide by 2.54. To convert kilograms to pounds, divide by 0.45.
Characteristics of waitlisted patients with PALF, as well as characteristics of PALF liver transplant recipients and their donors.
Race and ethnicity were reported by transplant centers to the SRTR and were assessed for this study as 2 factors. Response options for ethnicity were Hispanic and non-Hispanic, and response options for race were Asian or Pacific Islander, Black, Hispanic (for those indicating Hispanic ethnicity), Other (including multiracial or Native individuals), and White.
Includes multiracial patients and Native patients.
Includes patients that were transferred, removed, or whose record lists “other.”
Figure. Impact of Changes in Allocation and Waitlist Prioritization on Waitlist Mortality and Posttransplant Outcomes in Pediatric Acute Liver Failure.
A, Cumulative incidence of death while on the waitlist or within 90 days of removal, stratified by era. Era 1 patients had the highest rate of mortality while on the waitlist or within 90 days of removal (19.2%), while patients in era 3 had the lowest rate of mortality (7.2%; P < .001). B, Overall patient survival after LT for PALF, stratified by era. Patients in era 1 had the highest rate of mortality (39.6%), while patients in era 3 had the lowest rate of mortality (6.9%; P < .001). C, Graft survival after LT for PALF, stratified by era. Patients in era 1 had the highest rate of graft failure (33.1%), while patients in era 3 had the lowest rate of graft failure (6.6%; P = .01). LT indicates liver transplantation; PALF, pediatric acute liver failure.
Transplant
Median (IQR) patient age at LT was 5 (1-11) years (Table). LT recipients in era 3 were more likely to receive a whole liver (72%; P < .001), with shorter median (IQR) cold ischemic time in hours (6.5 [5.3-8.2]; P < .001), despite an increase in the median (IQR) distance in kilometers between donor and recipient hospitals from era 1 (182.9 [16.5-643.0]) to 3 (515.7 [108.6-1297.8]) (P < .001). Donors in era 3 were younger, with a median (IQR) age of 14 (3-27) years, had smaller median (IQR) heights (152 [99-170] cm) and weights (50 [17-69] kg), and were more likely to be deceased (95%) (Table). Long-term post-LT patient and graft survival were highest in era 3 (P < .001 and P = .01 at 5 years, respectively) (Figure, B and C).
Multivariate analysis revealed that age younger than 2 years (vs ≥10 years; subdistribution hazard ratio [sHR], 8.88; 95% CI, 2.11-36.49; P = .003), Hispanic ethnicity (vs non-Hispanic ethnicity; sHR, 0.08; 95% CI, 0.02-0.39; P = .002), and receipt of deceased donor split grafts (vs whole liver; sHR, 0.17; 95% CI, 0.05-0.58; P = .005) were associated with risk of mortality post-LT in era 1. This resolved by era 3 (P = .34, P = .10, and P = .27, respectively). Similarly, recipient age younger than 2 years (vs ≥10 years; sHR, 11.26; 95% CI, 2.01-63.24; P = .006) was associated with risk of graft failure in eras 1 and 2 (sHR, 4.89; 95% CI, 1.56-15.30; P = .006), which resolved by era 3 (P = .99).
Discussion
PALF is a rapidly progressive and life-threatening condition. Adequate waitlist prioritization, combined with allocation policies designed to increase the chance that children receive timely and high-quality organ offers, remains key to reducing mortality in PALF. This study demonstrates that policy changes are associated with substantially decreased pediatric waitlist mortality via increased rates of LT and improved posttransplant outcomes. This is likely related to the observation that policy changes were associated with children with PALF receiving organs from younger, smaller donors within a larger geographic range. With recipient demographics showing no association with post-LT mortality and graft failure since 2012, these policies appear to mitigate potential disparities in PALF. Also, risks associated with technical variant grafts decreased across eras, suggesting that surgical experience positively impacted survival outcomes (Table). Similarly, changes in practice, such as medical management of PALF and earlier referral to transplant centers, may have improved outcomes across the study period. These factors are not captured by the SRTR, which is a limitation of our analysis. Overall, this study supports the continued application of policies striving to eliminate waitlist mortality and increase rates of LT among children in the US with PALF.
eFigure 1. Timeline of UNOS Policy Changes Detailing Status Criteria/Definition and Liver Allocation Algorithms Across 3 Eras
eFigure 2. CONSORT Diagram of Inclusion/Exclusion Criteria
Data Sharing Statement
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eFigure 1. Timeline of UNOS Policy Changes Detailing Status Criteria/Definition and Liver Allocation Algorithms Across 3 Eras
eFigure 2. CONSORT Diagram of Inclusion/Exclusion Criteria
Data Sharing Statement
