Abstract
Background:
Transplants with hearts and lungs from donors with hepatitis C (HCV D+) have been proven safe and effective since development of direct-acting antivirals, yet the presence of HCV+ persists as a reason to decline organs.
Methods:
We identified adult candidates listed 1/1/2015–3/8/2023 for heart or lung transplant using the Scientific Registry of Transplant Recipients. We identified individual- and center-level characteristics associated with listing to consider HCV D+ offers using multilevel logistic regression in a multivariable framework.
Results:
Over the study period, the annual percentage of candidates willing to consider HCV D+ offers increased for both heart (9.5% to 74.3%) and lung (7.8% to 59.5%), as did the percentage of centers listing candidates for HCV D+ heart (52.9% to 91.1%) and lung (32.8% to 82.8%) offers. Candidates at centers with more experience with HCV D+ transplants were more likely to consider HCV D+ organ offers. After adjustment, listing center explained 70% and 78% of the residual variance in willingness to consider HCV D+ hearts and lungs, respectively.
Conclusions:
Although listing for consideration of HCV D+ offers has increased, it varies by transplant center. Center-level barriers to consideration of HCV D+ organs reduce recipients’ transplant access.
Keywords: heart transplant, lung transplant, hepatitis C, waitlist, outcomes
INTRODUCTION
The growing and persistent national organ shortage has necessitated innovative strategies to expand the donor pool for heart and lung transplants. In recent years, there has been reconsideration of the use of donor organs that would previously have been discarded, notably including organs from donors with hepatitis C virus (HCV D+). The development of HCV direct-acting antivirals (DAAs) with nearly 100% cure have made HCV D+ organs a viable allograft choice for HCV-seronegative waitlist candidates.1
The use of HCV D+ organs for HCV-seronegative transplant candidates has increased organ availability, increased patient access to transplant,2 and reduced waitlist time.3 Three-year follow-up data support the safety and effectiveness of using HCV D+ organs for HCV-seronegative heart and lung recipients.4,5 These studies have consistently found that transplants using HCV D+ organs have equivalent perioperative outcomes (acute rejection, hospital length of stay, etc.) and posttransplant mortality risk as transplants using organs from HCV-seronegative donors,4,5 with HCV cure.6 However, many centers continue to not list any or most transplant candidates as willing to consider offers from donors with hepatitis C. While this might be due to individual-level concerns about HCV-related stigma,7 past studies have suggested that the strongest predictor of candidate willingness to consider these offers is provider encouragement.8 Despite this evidence of the importance of provider and center influence on listing practices and evidence from our prior studies of the importance of listing practices on waitlist outcomes,9 however, center-level factors associated with willingness to consider heart or lung offers from donors with hepatitis C have not been evaluated.
As such, we examined trends in the willingness of adult heart and lung waitlist candidates to consider HCV D+ organ offers from 2015 to March 2023 using national registry data. We identified individual-level and center-level factors that were associated with listing as willing to consider HCV D+ offers for each organ type.
PATIENTS AND METHODS
Data source
This study used data from the United States Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donors, wait-listed candidates, and transplant recipients in the U.S., submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors. These data have been described elsewhere.10 This study complies with the ISHLT ethics statement and was approved by the Johns Hopkins Institutional Review Board (NA_00042871). This study was granted a waiver of informed consent given the use of deidentified registry data.
Study population
Using SRTR, we identified all adult candidates actively listed for heart or lung transplantation in the United States from January 1st, 2015 through March 8th, 2023. We ascertained candidate willingness to consider HCV D+ organ offers using donor acceptance criteria specified in the United Network for Organ Sharing (UNOS) database11 as of September 2023 (SRTR data release), which indicate a candidate’s willingness to consider HCV D+ organ offers. Waitlist candidate HCV serostatus was not available. For each organ type, we compared age at listing, sex, race, blood type, history of diabetes, body mass index (BMI), diagnosis for transplant, and other organ-specific variables between candidates willing and unwilling to consider HCV D+ organ offers using Wilcoxon rank-sum tests and Chi-square tests for continuous and categorical variables. Listing center was missing for 0.01% (n=4) candidates and thus, these candidates were excluded from the analyses.
Changes in willingness to consider HCV D+ organ offers
We calculated the percent of active heart and lung candidates listed as willing to consider HCV D+ organ offers annually over the study period. To determine if any changes were occurring nationally or within the same transplant centers, we calculated the percent of transplant centers with at least one candidate that was listed as willing to consider HCV D+ organ offers over the study period. We used a non-parametric test of trend to determine whether the percent of candidates or the percent of centers listing patients as willing changed from 2015 to 2022. For this descriptive analysis of annual trends, we did not include data from 2023, as the two months of data available prior to the lung allocation policy change on March 9th, 2023 are unlikely representative of the full year..
Center-level willingness to consider HCV D+ organ offers
To characterize centers listing patients as willing to consider HCV D+ organ offers in the most recent era, we considered only the last two years of data from 1/1/2021–3/8/2023 and categorized centers by quartile of percent of candidates that were listed as willing to consider HCV D+ organ offers. For each center and organ type, we determined annual waitlist volume, annual deceased donor transplant volume, annual living donor transplant volume, median time spent on the waitlist, number of centers in the region, number of organs recovered locally, ratio of organs recovered to annual waitlist volume, percent of adult recipients with HCV between 2015–2020, and number of transplants from donors with HCV to recipients without HCV (HCV D+/R-) from 2015–2020. Annual waitlist volume was defined as the average number of patients that spent any time on the waitlist at that center for the full years of 2021 and 2022. Time on the waitlist was defined as the amount of time prevalent and incident candidates spent on the waitlist until they were removed for transplant, death, or other reasons in 2021 and 2022. Organs recovered was defined as the total number of organs recovered by the local organ procurement organization between 2021–2023. We used a non-parametric tests of trend to determine bivariate associations between these factors and the percent of candidates listed as willing to consider HCV D+ organ offers at each center. Given that HCV D+ organ transplants were first performed in kidney and liver recipients and that experience might influence a center’s willingness to perform these transplants, we evaluated whether the likelihood of listing at least one candidate as willing to consider HCV D+ abdominal organ (kidney and/or liver) offers and cardiothoracic organ (heart and/or lung) offers were associated using a kappa statistic.
Factors associated with willingness to consider HCV D+ heart and lung offers
To understand individual- and center-level factors associated with listing as willing to consider HCV D+ heart and lung offers in a multivariable framework, we used multilevel logistic regression models with a random intercept for center.12 We assessed the functional form of continuous variables using Lowess curves and created categories where appropriate. Each model includes individual and center-level factors as fixed effects and a random intercept for each center to account for clustering and variation in willingness across centers. We report the intraclass correlation coefficient to understand how much of the variance in listing as willing to consider HCV D+ organ offers was explained by center. Finally, to characterize the extent of heterogeneity in this listing practice across centers, we report the median odds ratio for each model. The median odds ratio can be interpreted as the expected difference in the odds of being listed as willing to consider HCV D+ organ offers for any two similar candidates listing at any two different centers across the United States.
Statistical analysis
We used an α of 0.05 to determine statistical significance. All analyses were performed using Stata 17.0/MP for Windows (College Station, Texas).
RESULTS
Study population
We identified 56,462 waitlist candidates who were listed for a heart (N=32,663) or lung (N=23,799) by 113 heart and 64 lung centers between 1/1/2015–3/8/2023 (Table 1). Heart transplant candidates willing to consider HCV D+ organ offers were less likely to be female (25.3% vs. 27.5%, p<0.001) or listed as Status 1 (16.8% vs. 49.1%, p<0.001) and were more likely to be of blood type O (47.0% vs. 41.1%, p<0.001). Lung transplant candidates willing to consider HCV D+ organ offers were more likely to be female (42.7% vs. 41.4%, p=0.04), less likely to be of Black race (9.2% vs. 10.8%, p<0.001), and had a higher median (IQR) Lung Allocation Score (LAS) score [39 (35–47) vs. 39 (35–49), p=0.002].
Table 1.
Characteristics of Adult Heart and Lung Transplant Candidates, by Willingness to Consider Organ Offers from Donors with Hepatitis C, 1/1/2015–3/8/2023
| Heart | Lung | |||||
|---|---|---|---|---|---|---|
| Consider HCV D+ offers | No | Yes | P | No | Yes | P |
|
| ||||||
| N | 16,188 | 16,475 | 14,382 | 9,417 | ||
| Age at listing (years), median (IQR) | 56 (46–63) | 56 (46–63) | 0.19 | 61 (53–66) | 61 (53–67) | 0.01 |
| Female | 27.5% | 25.3% | <0.001 | 41.4% | 42.7% | 0.04 |
| Race | <0.001 | <0.001 | ||||
| White | 59.5% | 61.0% | 74.5% | 75.4% | ||
| Black | 24.7% | 25.9% | 10.8% | 9.2% | ||
| Hispanic | 10.8% | 8.4% | 10.9% | 11.1% | ||
| Other | 5.0% | 4.7% | 3.9% | 4.3% | ||
| Diagnosis | ||||||
| Heart | <0.001 | |||||
| Dilated | 81.6% | 80.4% | ||||
| Restrictive | 3.6% | 4.6% | ||||
| Ischemic | 4.1% | 3.8% | ||||
| Non-ischemic | 10.8% | 11.2% | ||||
| Lung | <0.001 | |||||
| Obstructive | 21.9% | 20.8% | ||||
| Pulmonary vascular | 5.9% | 5.6% | ||||
| Cystic fibrosis and immunodeficiency | 7.1% | 5.0% | ||||
| Restrictive | 65.1% | 68.5% | ||||
| Other | <1% | <1% | ||||
| Blood type | <0.001 | 0.09 | ||||
| O | 41.1% | 47.0% | 46.3% | 47.4% | ||
| A | 38.8% | 34.8% | 38.5% | 36.9% | ||
| B | 14.9% | 14.3% | 11.5% | 12.0% | ||
| AB | 5.2% | 3.9% | 3.7% | 3.8% | ||
| Diabetes mellitus | 30.3% | 30.8% | 0.33 | 21.0% | 18.5% | <0.001 |
| Status | <0.001 | |||||
| 1 | 49.1% | 16.8% | ||||
| 2 | 16.3% | 32.7% | ||||
| 3–6 | 16.3% | 37.2% | ||||
| Temporarily inactive | 18.3% | 13.3% | ||||
| Lung allocation score, median (IQR) | 39 (35–47) | 39 (35–49) | 0.002 | |||
Individual-level willingness to consider HCV D+ organ offers
Overall, 50.4% of adult heart candidates and 39.6% of adult lung candidates were listed as willing to consider HCV D+ organ offers. HCV offer interest varied over the study period for both organ types. From 2015 to 2022, HCV D+ offer interest increased from 9.5% to 74.3% for heart and from 7.8% to 59.5% for lung (Figure 1A) (p-values<0.001). These temporal trends were reflected in the number of HCV D+ organ transplants performed during that period, which rose from 0.9% to 11.5% for heart and from 0% to 7.1% for lung (Figure 1A) (p-values<0.001).
Figure 1. (A) Percent of candidates on the national waitlist listed as willing to consider (solid) or transplanted with (dashed) organs from donors with Hepatitis C and (B) Percent of centers with at least one candidate listed as willing to consider (solid) or transplanted with (dashed) organs from donors with Hepatitis C, by organ type, 1/2015–12/2022.
Center-level willingness to consider HCV D+ organ offers
The percent of transplant centers that had at least one adult candidate listed as willing to consider HCV D+ offers increased from 2015 to 2022 for both heart (52.9% vs. 91.1%, p<0.001) and lung (32.8% vs. 82.8%, p<0.001) (Figure 1B). These trends were similarly reflected in the number of centers performing any HCV D+ organ transplants during that period, which rose from 1.7% to 63.6% (p<0.001) for heart and from 0% to 62.5% (p<0.001) for lung (Figure 1B).
Among centers listing anyone as willing to consider HCV D+ offers for heart or lung, there was wide variation in the proportion of candidates that were listed as willing to consider HCV D+ organ offers (Figure 2). HT centers in the lowest quartile (n=29 centers) listed a median of 11.8% (IQR 0–22%) of their candidates as willing while HT centers in the highest quartile (n=28 centers) listed a median of 100% (99.7–100%) of their candidates as willing. 10 HT centers continued to list 0% of their candidates as willing. LT centers in the lowest quartile (n=16 centers) listed a median of 0.0% (IQR 0–7%) of their candidates as willing while LT centers in the highest quartile (n=16 centers) listed a median of 100% (100–100%) of their candidates as willing. 10 LT centers continued to list 0% of their candidates as willing to consider HCVD+ organs in the recent era (2021–2023).
Figure 2. Center-level variation in listing candidates as willing to consider organs from donors with Hepatitis C, 1/1/2021–3/8/2023.
Each dot represents a center; colors indicate each organ-specific quartile of percent of candidates listed as willing to consider organs from donors with Hepatitis C.
For heart centers, those listing a higher percentage of candidates as willing to consider HCVD+ hearts were more likely to have lower percentage of Hispanic patients, fewer HT centers in their region, more experience with HT recipients with HCV, and more experience with HTs using donors with HCV among recipients without HCV in the prior era (2015–2020) and the recent era (2021–2023) (Table 2A). For lung centers, those listing a higher percentage of candidates as willing to consider HCVD+ lungs were more likely to have fewer candidates on public insurance, and more experience with LTs using donors with HCV among recipients without HCV in the prior era (2015–2020) and the recent era (2021–2023) (Table 2B).
Table 2.
Center-Level Characteristics Stratified by Quartile of Percent of Candidates Listed as Willing to Consider Organs from Donors with Hepatitis C at that Center for (A) Heart and (B) Lung in the Recent Era, 1/1/2021–3/8/2023
| A) Heart | |||||
|---|---|---|---|---|---|
|
| |||||
| Quartile | |||||
| Center-level Factors | Q1 (Lowest) | Q2 | Q3 | Q4 (Highest) | p-value |
| Number of centers | 29 | 28 | 28 | 28 | |
|
| |||||
| % of candidates listed to consider HCV offers at a center, median (IQR) | 11.8 (0.0–22.0) | 72.7 (63.9–77.6) | 95.0 (93.1–97.1) | 100.0 (99.7–100.0) | <0.001 |
| Candidates over 65, median (IQR) | 16.9 (12.5, 22.6) | 15.1 (11.4, 19.9) | 17.6 (14.5, 20.9) | 20.0 (14.1, 25.5) | 0.16 |
| Black candidates, median (IQR) | 29.1 (19.7, 38.5) | 23.5 (17.8, 31.8) | 23.1 (14.0, 36.0) | 28.7 (12.1, 39.9) | 0.69 |
| Hispanic candidates, median (IQR) | 14.6 (3.4, 22.2) | 4.7 (2.1, 13.2) | 6.0 (2.5, 15.6) | 2.8 (1.3, 7.9) | 0.002 |
| Candidates on public insurance, median (IQR) | 58.1 (51.7, 66.7) | 52.2 (42.8, 60.6) | 54.0 (42.1, 59.2) | 52.1 (44.9, 60.8) | 0.06 |
| Median time on list (days), median (IQR) | 358(191–496) | 331(192–475) | 252(194–420) | 246 (153–417) | 0.15 |
| Annual waitlist volume, median (IQR) | 44 (20–82) | 56 (40–69) | 80 (55–98) | 45 (30–90) | 0.32 |
| Annual deceased donor HT volume, median (IQR) | 18 (8–35) | 25 (16–36) | 43 (21–57) | 24(13–41) | 0.09 |
| Number HT centers in region, median (IQR) | 13 (11–15) | 13 (11–15) | 12 (8–15) | 12 (10–14) | 0.03 |
| Organ supply, median (IQR) | 210(118–323) | 145 (97–213) | 203 (141–267) | 216 (137–297) | 0.60 |
| Organ supply-waitlist demand ratio, median (IQR) | 3.8 (2.5–7.5) | 2.8 (1.6–4.7) | 2.8 (1.7–4.0) | 3.4 (2.4–7.9) | 0.13 |
| HCV R+ HT, median (IQR) | 3 (1–5) | 3 (2–6) | 5(2–10) | 3 (1–7) | 0.12 |
| Percentage of HT with HCV D+, median (IQR) | 0.0 (0.0–1.7) | 5.8 (3.0–9.3) | 7.9 (5.6–17.3) | 9.7 (4.0–15.1) | <0.001 |
| HCV D+/R− HT 2015–2020, median (IQR) | 0 (0–1) | 2(0–12) | 9 (5–22) | 5(1–14) | 0.02 |
| HCV D+/R− HT 2021–2023 median (IQR) | 0 (0–2) | 6(2–10) | 13 (5–18) | 7(2–12) | <0.001 |
|
| |||||
| B) Lung | |||||
|
| |||||
| Quartile | |||||
| Center-level Factors | Q1 (Lowest) | Q2 | Q3 | Q4 (Highest) | p-value |
| Number of centers | 16 | 16 | 16 | 16 | |
|
| |||||
| % of candidates listed to consider HCV offers at a center, median (IQR) | 0.0 (0.0–6.9) | 42.5 (32.1–55.8) | 89.4(85.0–95.1) | 100.0 (100.0–100.0) | <0.001 |
| Candidates over 65, median (IQR) | 32.9 (25.7, 40.6) | 35.4 (29.4, 39.6) | 34.6 (28.8, 41.1) | 31.9 (27.8, 42.5) | 0.55 |
| Black candidates, median (IQR) | 10.3 (6.1, 15.3) | 9.9 (5.5, 16.0) | 10.9 (7.5, 13.8) | 8.3 (3.9, 15.3) | 0.62 |
| Hispanic candidates, median (IQR) | 8.8 (1.5, 29.9) | 12.3 (3.0, 28.5) | 5.4 (2.9, 9.3) | 10.2 (3.9, 19.4) | 0.16 |
| Candidates on public insurance, median (IQR) | 61.3 (55.3, 68.4) | 59.0 (52.7, 64.9) | 55.8 (49.8, 66.2) | 49.3 (45.9, 60.8) | 0.03 |
| Median time on list (days), median (IQR) | 179(100–241) | 139 (79–220) | 99(75–149) | 116(62–181) | 0.02 |
| Annual waitlist volume, median (IQR) | 47 (30–87) | 71 (47–107) | 52 (21–72) | 47 (34–103) | 0.68 |
| Annual deceased donor LT volume, median (IQR) | 27 (17–47) | 42 (28–68) | 34 (12–46) | 36 (18–64) | 0.79 |
| Number LT centers in region, median (IQR) | 7(6–8) | 7 (7–7) | 7 (7–8) | 7 (6–8) | 0.69 |
| Organ supply, median (IQR) | 151 (71–201) | 173(104–259) | 107(84–154) | 151 (127–213) | 0.81 |
| Organ supply-waitlist demand ratio, median (IQR) | 3.0 (1.5–4.5) | 2.2 (1.4–3.7) | 2.6 (1.6–4.6) | 3.2 (1.8–5.0) | 0.39 |
| HCV R+ LT, median (IQR) | 4 (2–8) | 9(5–16) | 5 (3–8) | 6 (4–17) | 0.49 |
| Percentage of LT with HCV D+, median (IQR) | 0.0 (0.0–0.2) | 2.1 (0.7–5.4) | 8.6 (3.9–12.0) | 4.1 (1.9–7.0) | 0.003 |
| HCV D+/R− LT 2015–2020, median (IQR) | 0 (0–0) | 1 (0–5) | 11(3–16) | 5(1–14) | 0.0491 |
| HCV D+/R− LT 2021–2023, median (IQR) | 0 (0–0) | 6 (2–11) | 7(2–10) | 6(4–13) | 0.001 |
There was slight agreement between a center listing at least one candidate as willing to consider HCV D+ abdominal organ (kidney and/or liver) offers and listing at least one candidate as willing to consider HCV D+ cardiothoracic organ (heart and/or lung) organ offers (kappa 0.16, p<0.001).
Factors independently associated with willingness to consider HCV D+ organ offers
Across organ types, individual-level fixed effects including age, sex, race/ethnicity, primary indication for transplant, and blood type were associated to varying degrees with listing as willing to consider HCV D+ organ offers (Table 3). While multiple center-level fixed effects were associated with listing as willing to consider HCV D+ organ offers for lung transplant centers, including annual waitlist volume, annual transplant volume, and median LAS at center, these associations were not significant for heart transplant centers.
Table 3.
Individual and center-level factors associated with listing as willing to consider organs from donor with Hepatitis C among (A) heart and (B) lung transplant candidates in the recent era, 1/1/2021–3/8/2023
| A. Heart | ||
|---|---|---|
|
| ||
| Characteristic | aOR (95% CI) of listing as willing to consider HCV D+ | P-value |
|
| ||
| Individual-level factors | ||
| Age | ||
| 18–40 | (Reference) | |
| 41–50 | 1.38 (1.08–1.76) | 0.009 |
| 51–60 | 1.34 (1.08–1.66) | 0.008 |
| >60 | 1.52 (1.23–1.89) | <0.001 |
| Female (vs male) | 0.81 (0.69–0.96) | 0.01 |
| Race/Ethnicity | ||
| White | (Reference) | |
| Black | 0.82 (0.69–0.98) | 0.03 |
| Hispanic | 0.66 (0.51–0.85) | 0.001 |
| Other | 0.58 (0.42–0.81) | 0.002 |
| Disease etiology | ||
| Dilated | (Reference) | |
| Restrictive | 0.79 (0.56–1.12) | 0.18 |
| Ischemic | 1.52 (0.99–2.35) | 0.06 |
| Non-Ischemic | 0.83 (0.66–1.05) | 0.12 |
| Status | ||
| 1 | (Reference) | |
| 2 | 1.06 (0.81–1.37) | 0.68 |
| 3–6 | 0.95 (0.73–1.24) | 0.70 |
| Temporarily Inactive | 0.64 (0.47, 0.88) | 0.005 |
| Blood type | ||
| O | (Reference) | |
| A | 0.69 (0.59–0.81) | <0.001 |
| B | 0.83 (0.66–1.03) | 0.10 |
| AB | 0.43 (0.31–0.61) | <0.001 |
|
| ||
| Center-level factors | ||
| Annual waitlist volume | 0.99 (0.96–1.02) | 0.56 |
| Annual deceased-donor transplant volume (per unit increase) | 1.02 (0.96–1.08) | 0.61 |
| Median waitlist time (per day) | 0.999 (0.995,1.00) | 0.93 |
| Prior experience with HCV R+ HT recipients (per person), 2015–2020 | 0.97 (0.83–1.14) | 0.73 |
| Prior experience with HCV D+/R− HTs (ever), 2015–2020 | 55.59 (14.85–208.15) | <0.001 |
|
| ||
| Median odds ratio | 13.86 (7.42–20.30) | <0.001 |
|
| ||
| Intraclass correlation coefficient | 0.70 (0.62–0.77) | |
|
| ||
| B. Lung | ||
|
| ||
| Characteristic | aOR (95% CI) of listing as willing to consider HCV D+ | P-value |
|
| ||
| Individual-level factors | ||
| Age | ||
| 18–40 | (Reference) | |
| 41–50 | 1.18 (0.81–1.71) | 0.88 |
| 51–60 | 1.10 (0.80–1.51) | 0.58 |
| >60 | 1.04 (0.76–1.41) | 0.22 |
| Female (vs male) | 1.48 (1.26–1.74) | <0.001 |
| Race/Ethnicity | ||
| White | (Reference) | |
| Black | 0.82 (0.63–1.07) | 0.14 |
| Hispanic | 1.01 (0.78–1.30) | 0.96 |
| Other | 0.83 (0.57–1.23) | 0.35 |
| Disease etiology | ||
| Obstructive | (Reference) | |
| Pulmonary vascular | 1.06 (0.73–1.54) | 0.74 |
| Cystic fibrosis and immunodeficiency | 1.12 (0.57–2.21) | 0.74 |
| Restrictive | 1.07 (0.86–1.33) | 0.55 |
| Lung allocation score (per unit) | 1.00 (0.99, 1.00) | 0.44 |
| Blood type | ||
| O | (Reference) | |
| A | 0.93 (0.78–1.10) | 0.39 |
| B | 1.02 (0.79–1.32) | 0.88 |
| AB | 0.88 (0.58–1.34) | 0.57 |
|
| ||
| Center-level factors | ||
| Annual waitlist volume (per candidate) | 0.94 (0.88–0.998) | 0.04 |
| Median LAS of listed candidates | 0.58 (0.36–0.96) | 0.04 |
| Median annual deceased-donor transplant volume (per unit increase) | 1.11 (1.00–1.22) | 0.04 |
| Prior experience with HCV R+ LT recipients (per person), 2015–2020 | 1.09 (0.86–1.40) | 0.47 |
| Prior experience with HCV D+/R− LTs (ever), 2015–2020 | 348.64 (46.16–2633.36) | <0.001 |
|
| ||
| Median odds ratio | 25.32 (4.06–46.58) | 0.02 |
|
| ||
| Intraclass correlation coefficient | 0.78 (0.67–0.85) | |
The predominant center-level factor that emerged from the multivariable models related to a center’s experience with HCV D+/R− transplants prior to 2020 (2015–2019). Listing at a heart or lung center that had performed at least one HCV D+/R− in 2015–2019 was associated with 56-fold or 349-fold higher odds of willingness to consider HCV D+ organs, respectively (Tables 3A and 3B). After adjusting for candidate-- and center-level factors, listing center explained approximately 70% and 78% of the total residual variance in listing as willing to consider HCV D+ hearts and lungs, respectively.
For heart transplant candidates, the median odds ratio associated with willingness to consider HCV D+ offers was 13.86 (95% CI 7.42–20.30, p<0.001), indicating that any two similar heart transplant candidates listed at any two similar heart transplant centers across the United States could expect a nearly 14-fold difference in their chance of being listed as willing to consider an HCV D+ heart, driven by center alone (Table 3A). Similarly, lung candidates listing at centers across the US could expect a more than 25-fold difference in their chances of being listed as willing to consider HCV D+ organ offers driven by center alone (median odds ratio 25.32, 95% CI 4.06–46.58, p=0.02, Table 3B).
DISCUSSION
In this national study of willingness to consider HCV D+ organ offers for adult heart and lung transplant candidates, we found that the percentage of candidates listed to consider HCV D+ offers increased from 2015 through March 2023 but remained below 75% for both lung and heart candidates. Additionally, the percentage of transplant centers listing at least one adult candidate to consider HCV D+ offers increased to 83% for lung centers and 91% for heart centers. However, several of the highest-volume centers listed few candidates for consideration of HCV D+ offers, despite evidence of the safety and benefit of this practice.4,5,9 The strongest factor associated with a candidate being listed as willing to consider HCV D+ organ offers was the center’s experience with HCV D+/R− transplants; this increased the odds of a candidate being listed as willing to consider HCV D+ organ offers by 56 times for heart and by 349 times for lung.
While candidates must sign an HCV-specific consent to be listed in UNOS as willing to consider HCV D+ organ offers, we found that center-level factors were the strongest predictors of HCV offer listing practices. Specifically, the strongest predictor of listing to consider an HCV D+ offer was whether the center had previously performed transplants from a HCV D+ to a seronegative recipient. Even after adjusting for available candidate and center characteristics, the center a candidate was listed at explained 70–78% of the remaining variability in listing practices. Our finding that center-level practice was critically important is consistent with the findings of Prakash et al. in interviews with solid organ transplant recipients who had donor-derived HCV infections, in which trust in their physician’s recommendation was one of the most important reasons they accepted an HCV D+ organ offer.8 Physician confidence is critical to creating patient confidence in and increasing adoption of the use of HCV D+ organs for transplantation, including for HCV-seronegative candidates. This finding is also consistent with prior literature about HCV D+ transplants in liver transplantation, where Cotter et al. noted a 6-fold difference in practice between UNOS regions.13 These findings underscore the need for greater education of transplant providers and changes in center-level practice nation-wide and across organ types. We also found that multiple centers listed 100% of their candidates as willing to consider HCV D+ offers, suggesting that some centers have adopted a policy of listing all candidates for consideration of HCV D+ offers. Given that willingness to consider HCV D+ offers does not require acceptance of an HCV D+ offer, this strategy broadens the pool of potential donors for a candidate. This broader pool of potential donors was likely a driving factor in the lower waitlist mortality that our group observed among lung transplant candidates who were listed as willing versus not willing to consider HCV D+ offers.9 Our finding in this study that center experience with HCV D+/R− transplants increased the odds of a candidate being listed as willing to consider HCV D+ organ offers by up to 349-fold further suggests that centers who perform one of these transplants realize the benefit of utilizing this donor pool and are more willing to encourage future candidates to consider HCV D+ offers.
The increase in the percentage of waitlist candidates listed as willing to consider HCV D+ organ offers that we observed is consistent with previously reported trends from 2015 to 2018 after DAAs for all major types of solid organ transplants.13,14 Our finding that the percentage of candidates listed as willing to consider HCV D+ heart and lung offers has continued to increase is highly encouraging, as is the increase in the percentage of heart and lung transplant centers listing candidates as willing to consider HCV D+ offers. However, 26% and 40% of heart and lung candidates, respectively, are not listed as willing to consider HCV D+ offers, and 9% and 17% of heart and lung centers currently do not have a single candidate listed as willing to consider HCV D+ offers, including medium- and high-volume centers. This limits the access to transplant for patients at these centers. Additionally, simulations in which all heart transplant candidates were willing to accept HCV D+ offers found that the number of transplants increased and there were fewer delistings and waitlist deaths, providing further evidence for the increase in access to transplant through use of HCV D+ organs.15 Together, these findings highlight the need to understand center-level barriers to listing candidates for consideration of HCV D+ offers with the goal of increasing the percentage of candidates listed for HCV D+ offers to optimize candidate access to transplantation.
This study used registry data, which limited our ability to truly separate the role that individual candidates versus providers versus centers play in decision-making related to HCV D+ organ offers. While we recognize that the candidates must ultimately approve being listed for consideration of HCV D+ offers, our analyses suggest that center-level practice is the dominant factor in determining listing practices. Additionally, we acknowledge that there are no long-term data on HCV D+/R− transplant outcomes, although 3-year outcomes data are highly promising. However, we agree that it is important to continue monitoring post-transplant outcomes of transplants with HCV D+ organs as this practice continues to expand. Due to the current donor acceptance criteria options, in which both HCV antibody-positive and viremic donors are considered HCV D+, we were unable to evaluate whether HCV-viremic offers were as likely to be considered as those that were antibody-positive only. However, studies in kidney transplantation have noted that odds discard of HCV-viremic kidneys have decreased from 5 times as high as for non-viremic kidneys to approximately 1.5 times as high, and that these kidneys are associated with excellent outcomes similar to those of non-viremic kidneys.7,16,17 This suggests that there is increasing acceptance and consideration of HCV-viremic organs for transplantation. Furthermore, studies in heart and lung transplantation have noted excellent outcomes of transplants with HCV-viremic organs.4,5 Finally, we were unable to study the willingness of candidates with versus without HCV infection, as SRTR does not include candidate HCV status in their candidate database. However, the majority of lung and heart recipients in the United States are HCV-seronegative, suggesting that the majority of the waitlist is also HCV-seronegative.
CONCLUSIONS
In conclusion, we found that the percentage of candidates listed as willing to consider HCV D+ offers has increased, but that over a quarter of candidates are still listed to never hear about HCV D+ offers. This highlights the opportunity to understand obstacles to listing candidates for consideration of HCV D+ offers at both the individual and center levels. However, given our finding that center-level practice appears to drive most of the variability in listing practices for consideration of HCV D+ offers, we believe that reducing center-level barriers might have the strongest impact on listing practices and encourage future research to identify these barriers.
Figure 3. Total number of adult candidates listed overall versus listed as willing to consider organs from donors with hepatitis C for (A) heart and (B) lung transplant centers in the United States, 1/1/2021–3/8/2023.
Each pair of bars represents one center, sorted according to total adult waitlist volume 1/1/2021–3/8/2023. The blue bars (top half of the graph) show the overall waitlist volume, while the red bars (bottom half of the graph) show the number of candidates listed as willing to consider organs from donors with hepatitis C.
ACKNOWLEDGMENTS
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; grant number K24DK101828, PI: Segev), the National Institute of Aging (NIA; F32AG06764209, PI: Ruck), and the National Heart Lung and Blood Institute (grant number F30HL168842, PI: Bowring). The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.
The data reported here have been supplied by the Hennepin Healthcare Research Institute (HHRI) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government.
GLOSSARY OF ABBREVIATIONS: (in order of appearance)
- HCV
hepatitis C virus
- HCV D+
donor with hepatitis C
- SRTR
Scientific Registry of Transplant Recipients
- OPTN
Organ Procurement and Transplantation Network
- HRSA
Health Resources and Services Administration
- UNOS
United Network for Organ Sharing
- BMI
body mass index
- HCV D+/R-
transplant from a donor with hepatitis C to a recipient without hepatitis C
- LAS
Lung Allocation Score
Footnotes
DISCLOSURES
DS has received support from consulting fees from AstraZeneca, CareDx, Moderna Therapeutics, Novavax, Regeneron, and Springer Publishing, as well as speaker honoraria from AstraZeneca, CareDx, Houston Methodist, Northwell Health, Optum Health Education, Sanofi, and WebMd. None of these were directly related to this study. The other authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.
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