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Address for reprints: Errol L. Bush, MD, Department of Surgery, Johns Hopkins Medical Institutions, Blalock 240, 600 North Wolfe St, Baltimore, MD 21287.
The feasibility and 6-month outcome safety of lung transplants (LTs) from hepatitis C virus (HCV)-viremic donors for HCV-seronegative recipients (R–) were established in 2019, but longer-term safety and uptake of this practice nationally remain unknown.
Methods
We identified HCV-seronegative LT recipients (R–) 2015-2020 using the Scientific Registry of Transplant Recipients. We classified donors as seronegative (D–) or viremic (D+). We used χ2 testing, rank-sum testing, and Cox regression to compare posttransplant outcomes between HCV D+/R– and D–/R– LT recipients.
Results
HCV D+/R– LT increased from 2 to 97/year; centers performing HCV D+/R– LT increased from 1 to 25. HCV D+/R– versus HCV D–/R– LT recipients had more obstructive disease (35.7% vs 23.3%, P < .001), lower lung allocation score (36.5 vs 41.1, P < .001), and longer waitlist time (P = .002). HCV D+/R– LT had similar risk of acute rejection (adjusted odds ratio [aOR], 0.87; P = .58), extracorporeal membranous oxygenation (aOR, 1.94; P = .10), and tracheostomy (aOR, 0.42; P = .16); similar median hospital stay (P = .07); and lower risk of ventilator > 48 hours (aOR, 0.68; P = .006). Adjusting for donor, recipient, and transplant characteristics, risk of all-cause graft failure and mortality were similar at 30 days, 1 year, and 3 years for HCV D+/R– versus HCV D–/R– LT (all P > .1), as well as for high- (≥20/year) versus low-volume LT centers and high- (≥5/year) versus low-volume HCV D+/R– LT centers (all P > .5).
Conclusions
HCV D+/R– and HCV D–/R– LT have similar outcomes at 3 years posttransplant. These results underscore the safety of HCV D+/R– LT and the potential benefit of expanding this practice further.
Lung transplants from donors with and without HCV viremia into recipients without HCV have similar risk of acute rejection, mortality, and all-cause graft failure at 3 years posttransplant.
Hepatitis C–viremic donors represent a growing portion of the donor pool, mostly due to intravenous drug abuse associated with the ongoing opioid epidemic. Understanding the long-term safety of lung transplants from hepatitis C–viremic donors into hepatitis C–seronegative recipients is critical to encourage uptake of this practice, which will further expand the donor pool and access to transplantation.
As with other solid-organ transplants, there are ongoing efforts to increase the pool of donor lungs available to transplant candidates to decrease waitlist time and mortality while maintaining survival benefit. While remarkable improvements have been made over the last decade, nearly 5000 people remain on the lung transplant waitlist,
These circumstances underscore the need for continued reevaluation of potential donor organs to address the organ shortage.
In 2013, the introduction of direct-acting antivirals (DAAs) to cure hepatitis C (HCV) infection reopened the possibility of using organs from HCV-viremic donors (D+) for HCV-seronegative recipients (R–).
HCV D+/R– cardiothoracic transplantation had previously been attempted, but this practice was stopped after studies showed approximately 3-fold greater risk of mortality.
Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation.
Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients: an open-label nonrandomized trial.
prompted reconsideration of this practice in cardiothoracic transplant. This is particularly relevant given increases in the HCV D+ population due to the opioid epidemic.
found that HCV D+/R– heart and lung transplants were feasible and had similar short-term safety as HCV D–/R– transplants but showed a potentially greater risk of acute rejection associated with HCV D+/R–. Evaluation of the same cohort of 44 patients at 12 months showed similar graft and patient survival but was limited by sample size.
Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.
Based on this evidence, the International Society for Heart and Lung Transplantation released an expert consensus statement regarding HCV D+/R– transplants that noted the benefit of these organs in terminally ill patients but noted the paucity of longer-term outcomes data, which limited their ability to gauge the safety of these transplants.
It is unknown how this tempered enthusiasm for HCV D+/R– transplants has affected the uptake of this practice across transplant centers.
Using national registry data, we evaluated trends in the annual number of HCV D+/R– transplants and the number of transplant centers performing HCV D+/R– transplants (Figure 1). We also compared outcomes of acute rejection, mortality, and all-cause graft failure to 3 years for HCV D+/R– versus HCV D–/R– lung transplants.
Figure 1Trends in use and outcomes of HCV-positive donor lungs for HCV-negative recipients from 2015 to 2020. HCV, Hepatitis C virus.
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 United States, submitted by the members of the Organ Procurement and Transplantation Network. The Health Resources and Services Administration, US Department of Health and Human Services provides oversight to the activities of the Organ Procurement and Transplantation Network and SRTR contractors. These data have been described elsewhere.
Using SRTR data, we identified all HCV-seronegative adult (≥18 years old) lung transplant (LT) recipients (R–) in the United States from January 2015 through December 2020. We restricted our time period to 2020 to ensure that follow-up data were available for all transplants. We classified recipients as seronegative if they had a negative HCV antibody test. We then classified donors as seronegative (D–) or viremic (D+). Viremic donors had a reactive HCV nucleic acid test. We excluded donors who had a positive HCV antibody test but a negative HCV nucleic acid test. There were no transplants in which the donor or recipient HCV status was unknown. We excluded recipients of previous transplants or “lobar” lung transplants (Figure 2). This study was deemed exempt for the need for institutional review board approval by the Johns Hopkins Institutional Review Board (NA_00042871).
Figure 2Identification of study population. HCV, Hepatitis C virus; Ab+, antibody positive; NAT, nucleic acid test.
Temporal Trends in the Use of Lungs From HCV-Viremic Donors for Transplant
We quantified the number of lung transplants from HCV-viremic donors to HCV-seronegative recipients (HCV D+/R–) performed in each year. We also quantified the number of centers performing HCV D+/R– lung transplants in each year. Transplant centers were defined as high-volume if they performed at least an average of 20 lung transplants per year during the study period. This cutoff was chosen because it has been used as a threshold to determine high-volume centers for both lung transplant and other complex thoracic surgeries.
Given the rapidly changing number of HCV D+/R– transplants by center, transplant centers were defined as high-volume for HCV D+/R– transplants if they performed at least 5 HCV D+/R– transplants in any year.
Donor and Recipient Characteristics
We compared the donor, recipient, and transplant characteristics of HCV D+/R– transplants and HCV-seronegative donor HCV-seronegative recipient (HCV D–/R–) transplants using χ2 and Wilcoxon rank-sum testing. We empirically included donor age, sex, race, and smoking history (≥20 vs <20 pack-years); recipient age, sex, race, and lung allocation score (LAS)
; and the type of transplant (unilateral vs bilateral lung transplant) as covariates in our multivariable model. Of the empirically included covariates, only donor smoking history had missing values (N = 212); these patients were excluded. Of note, waitlist time for recipients was unable to be separated into time before and after deciding to consider HCV-positive donor organ offers. Therefore, only total waitlist time was reported.
Posttransplant Outcomes
We studied incidence of posttransplant outcomes including acute rejection, extracorporeal membranous oxygenation (ECMO), tracheostomy, prolonged ventilator support (>48 hours), length of stay, mortality, and all-cause graft failure (ACGF; ACGF is a composite of mortality, graft loss, or retransplantation). In SRTR, mortality and graft loss are reported by individual transplant centers, and ascertainment is supplemented through linkage to the Social Security Master Death File (mortality) and the waiting list (graft loss).
For posttransplant outcomes available in SRTR as binary variables, including acute rejection, ECMO, prolonged ventilator support, and tracheostomy, we compared the proportion of HCV D+/R– and HCV D–/R– LT recipients who experienced the outcome during the study period using χ2 testing. For each outcome, a sensitivity analysis was performed including only transplants since 2017 to reduce the likelihood that differences in accrued follow-up time between the groups affected results, as well as to ensure inferences remained the same after the national experience of the first 2 years of HCV D+/R– transplants (a management “learning curve” period). Posttransplant length of stay was analyzed as a continuous variable, with comparison of the distribution of length of stay between groups using Wilcoxon rank-sum testing.
For mortality and ACGF, we performed time-to-event analysis and visualized the incidence of each outcome using Kaplan–Meier curves. We used Cox regression to compare the time to death or ACGF among HCV D+/R– versus HCV D–/R– transplants, adjusting for donor, recipient, and transplant characteristics chosen a priori, as described previously. As a sensitivity analysis, we also performed multilevel modeling to account for center-level clustering. We followed recipients until the outcome of interest or administrative censorship on February 28, 2022. For patients who died during the study period, cause of death was classified as due to graft failure, infection, cardiovascular, pulmonary, cerebrovascular, hemorrhagic, or other causes. Hepatitis C infection was not available as a cause of death, but both viral hepatitis and liver failure as causes of death were specifically evaluated. All analyses were performed using Stata 16.1/SE for Windows (StataCorp LLC).
Results
Practice of HCV D+/R– Lung Transplantation
The first HCV D+/R– LT was performed in 2016. The number of HCV D+/R– LT increased from 2 in 2016 to 97 in 2020. From 2019 to 2020, 207 HCV D+/R– LT transplants were performed, representing 4.4% of all LT performed during that time period (Figure 3). The number of transplant centers performing HCV D+/R– LT increased over the same period, from 1 in 2016 to 25 in 2020 (Figure 4). In 2020, 41.0% of all the centers that performed LTs were also performing HCV D+/R– LT. Among high-volume LT centers, 20 of 43 (46.5%) performed HCV D+/R– LT. Among low-volume LT centers, 6 of 27 (22.2%) performed HCV D+/R– LT.
Figure 3Number of lung transplants from HCV-viremic donors for HCV-seronegative recipients performed in the United States, by year, 2015-2020. Trend in total number of transplants per year indicated by the red line. HCV, Hepatitis C virus; D+/R–, HCV-viremic donor and HCV-seronegative recipient.
Figure 4Number of US transplant centers performing lung transplants from HCV-viremic and HCV-seronegative donors into HCV-seronegative recipients, by year, 2015-2020. Of note, the number of transplant centers performing HCV D–/R– lung transplants is equivalent to the total number of transplant centers performing lung transplants in a given year. HCV, Hepatitis C virus; HCV D–/R–, donor and recipient both HCV-seronegative; D+/R–, HCV-viremic donor and HCV-seronegative recipient.
Donor age was similar between groups, whereas donors in HCV D+/R– LT were less likely to be male (52.6% vs 60.8%, P = .006) and more likely to be of White race (81.6% vs 60.5%, P < .001), to die of anoxic brain injury (69.1% vs 29.2%, P < .001), and to have a ≥20 pack-year smoking history (16.9% vs 7.3%, P < .001; Table 1) than for HCV D–/R– LT.
Table 1Donor, recipient, and transplant characteristics by donor and recipient HCV status
Characteristic
HCV D–/R–
HCV D+/R–
P value
N
12,736
272
Donor characteristics
Age, y, median (IQR)
33 (24, 47)
32 (28, 38)
.18
Male sex
60.8%
52.6%
.006
White race
60.5%
81.6%
<.001
≥20 pack-year smoking history
7.3%
16.9%
<.001
Donation after circulatory death
5.0%
3.7%
.32
Recipient characteristics
Age, y, median (IQR)
61 (53, 67)
61 (54, 67)
.58
Male sex
59.3%
54.4%
.10
White race
78.6%
84.9%
.04
Blood type
O
45.1%
45.6%
>.87
A
39.5%
40.1%
B
11.4%
11.4%
AB
4.0%
2.9%
Diagnosis
Obstructive
23.3%
35.7%
<.001
Pulmonary vascular
4.9%
5.5%
Cystic fibrosis and immunodeficiency
8.9%
4.0%
Restrictive
39.6%
33.1%
Other
23.3%
21.7%
On ventilator pretransplant
5.0%
2.6%
.07
Waitlist time, d, median (IQR)
48 (14, 149)
57 (21, 203)
.002
Lung allocation score, median (IQR)
41.1 (35.2, 54.0)
36.5 (33.8, 45.9)
<.001
Lung allograft ischemia time, h, median (IQR)
5.4 (4.4, 6.5)
5.9 (4.9, 6.8)
<.001
Bilateral lung transplant
73.9%
82.7%
<.001
HCV, Hepatitis C virus; HCV D–/R–, Donor and recipient both HCV-seronegative; HCV D+/R–, HCV-viremic donor and HCV-seronegative recipient; IQR, interquartile range.
Obstructive lung disease was more common among HCV D+/R– LT recipients (35.7% vs 23.3%, P < .001). Waitlist time was longer for HCV D+/R– LT recipients (median 57 vs 48 days, P = .002). Recipients of HCV D+/R– LT had a lower median LAS than recipients of HCV D–/R– LT (36.5 vs 41.1, P < .001) and were more likely to receive a bilateral lung transplant (82.7% vs 73.9%, P = .001). Donor allografts in HCV D+/R– transplants had a median ischemic time that was 26 minutes longer than for allografts in HCV D–/R– transplants (P < .001). Recipient characteristics were otherwise similar between groups. Median (interquartile range) follow-up time was 3.1 (1.7, 4.7) years for HCV D–/R– transplants and 2.3 (1.6, 2.9) years for HCV D+/R– transplants.
Transplant Hospitalization Outcomes
Post-LT, the proportion of HCV D+/R– and HCV D–/R– LT recipients that required ECMO was similar (5.2% vs 5.7%, P = .72). The odds of post-LT ECMO were also similar for HCV D+/R– and HCV D–/R– LT (odds ratio [aOR], 1.94, 95% CI 0.89-4.22, P = .10) after adjusting for donor, recipient, and transplant characteristics. HCV D+/R– LT recipients were less likely to require prolonged ventilator support (29.9% vs 38.7%, P = .003); this inference remained unchanged in an adjusted model (HCV D+/R– vs HCV D–/R–: aOR, ventilator 0.68; 95% confidence interval [CI], 0.52-0.89; P = .006). HCV D+/R– LT recipients were less likely than HCV D–/R– recipients to require tracheostomy in an unadjusted analysis (1.1% vs 3.6%, P = .03); however, this difference was no longer significant in an adjusted model (aOR, 0.43; 95% CI, 0.13-1.39; P = .16). These inferences were unchanged in a sensitivity analysis restricted to LT performed since 2017. Median (interquartile range) hospital length of stay was similar for HCV D+/R– and HCV D–/R– recipients (17 [12, 29] vs 18 [12, 30] days, P = .21). This inference remained unchanged in an adjusted model (HCV D+/R– vs HCV D–/R– LOS difference –3.8 days, 95% CI, –7.9-0.2; P = .07). A sensitivity analysis restricted to LT performed since 2017 found that HCV D+/R– LT were associated with a 4.6-day shorter length of stay (95% CI, 0.4-8.9 days, P = .03).
Acute Rejection
The proportion of recipients experiencing acute rejection was similar among HCV D+/R– and HCV D–/R– LT (7.0% vs 7.9%, P = .58). After we adjusted for donor, recipient, and transplant characteristics, the odds of acute rejection were similar for HCV D+/R– and HCV D–/R– LT (aOR, 0.87; 95% CI, 0.54-1.41; P = .58; Table E1). A sensitivity analysis performed on LT since 2017 had similar results.
Mortality
The risk of mortality for HCV D+/R– versus HCV D–/R– LT was similar at 30 days (adjusted hazard ratio [aHR], 0.32; 95% CI, 0.08-1.28; P = .11), 1 year (aHR, 0.80; 95% CI, 0.52-1.22; P = .31), and 3 years (aHR, 0.94; 95% CI, 0.71-1.24; P = .66) posttransplant after adjusting for donor, recipient, and transplant characteristics (Figure 5 and Table E2). There were no significant differences in mortality for HCV D+/R– LT when comparing centers performing ≥20 to <20 LT per year (HR, 1.31; 95% CI, 0.52-3.31; P = .58), or when comparing centers that had performed ≥5 HCV D+/R– LT in a year to those that had lower HCV D+/R– LT volumes (HR, 0.87; 95% CI, 0.39-1.94; P = .74). A sensitivity analysis accounting for potential center-level clustering showed no difference in mortality between recipients of HCV D+/R– and HCV D–/R– transplants. There was no change in point estimates to suggest center-level effects on mortality.
Figure 5Mortality among recipients of HCV-viremic and HCV-seronegative lung transplants in the United States, 2015-2020, by years since transplant. HCV, Hepatitis C virus; HCV D–/R–, donor and recipient both HCV-seronegative; D+/R–, HCV-viremic donor and HCV-seronegative recipient; CI, confidence interval; aHR, adjusted hazard ratio.
The risk of ACGF for HCV D+/R– versus HCV D–/R– LT was similar at 30 days (aHR, 0.31; 95% CI, 0.08-1.25; P = .0.10), 1 year (aHR, 0.80; 95% CI, 0.53-1.22; P = .30), and 3 years (aHR, 0.93; 95% CI, 0.71-1.22; P = .59) posttransplant after adjusting for donor, recipient, and transplant characteristics (Figure 6 and Table E3). There were no significant differences in ACGF for HCV D+/R– LT when comparing centers performing ≥20 to <20 LT per year (HR, 1.11; 95% CI, 0.48-2.61; P = .80), or when comparing centers that had performed ≥5 HCV D+/R– LT in a year to those that had lower HCV D+/R– LT volumes (HR, 0.91; 95% CI, 0.41-2.02; P = .81). A sensitivity analysis accounting for potential center-level clustering showed no difference in mortality between recipients of HCV D+/R– and HCV D–/R– transplants. There was no change in point estimates to suggest center-level effects on ACGF.
Figure 6All-cause graft failure (ACGF) among recipients of HCV-viremic and HCV-seronegative lung transplants in the United States, 2015-2020, by years since transplant. HCV, Hepatitis C virus; HCV D–/R–, donor and recipient both HCV-seronegative; D+/R–, HCV-viremic donor and HCV-seronegative recipient; CI, confidence interval; aHR, adjusted hazard ratio.
Of the 4276 patients who died during the study period, 4224 received HCV D–/R– transplants and 52 received HCV D+/R– transplants. Overall, 91.2% had an available cause of death. For those with an available cause of death, there were no significant differences in cause of death between recipients of HCV D+/R– and HCV D–/R– transplants (P = .32). Causes of death included graft failure (HCV D+/R– vs HCV D–/R– 17.5% vs 8.7%), infection (16.9% vs 19.6%), cardiovascular (8.4% vs 8.8%), pulmonary (20.8% vs 23.9%), cerebrovascular (3.4% vs 6.5%), hemorrhagic (1.9 vs 4.4%), and other (32.1% vs 28.3%). No patients had viral hepatitis listed as a cause of death. A total of 25 patients (0.2%) had liver failure as a cause of death, all of whom had received HCV D–/R– transplants.
Discussion
In this national study of utilization and mid-term outcomes of HCV D+/R– lung transplants, we found that the number of HCV D+/R– transplants has risen almost exponentially since 2016, as has the number of centers performing HCV D+/R– lung transplants. Compared with HCV D–/R– lung transplants, HCV D+/R– transplants had statistically similar risk of mortality and ACGF at 30 days, 1-year, and 3 years posttransplant and of acute rejection, posttransplant ECMO, and tracheostomy. In addition, HCV D+/R– transplant recipients had similar hospital length of stay overall but a significantly shorter hospital length of stay for LT performed since 2017 compared with HCV D–/R– transplant recipients. These findings demonstrate favorable outcomes and mid-term safety of HCV D+/R– transplants and an encouraging uptake of this practice by transplant centers.
Our finding that HCV D+/R– lung transplants have similar mid-term outcomes to HCV D–/R– transplants is highly encouraging and consistent with literature on HCV D+/R– versus D–/R– kidney transplants.
While this technique was pioneered in kidney and liver transplants, all solid-organ transplants face a similar shortage of donors to treat growing candidate waitlists and benefit from this expansion of the donor pool. Still, the use of HCV D+/R– transplants remains novel for all types of solid organ transplant, and longer-term outcomes should continue to be monitored, particularly in organs such as kidney and liver with median graft survivals greater than 10 years. Our finding that HCV D+/R– LT had equivalent outcomes despite a 26-minute-longer median ischemic time might reflect higher HCV D+ versus D– organ quality; this warrants further study in a database with more granular donor organ quality information. In addition, we observed a greater percentage of HCV-viremic versus HCV-seronegative donors with a ≥20-pack year smoking history (16.9% vs 7.3%, P < .001) without evidence of negative effect on recipient transplant outcomes. While the impact of donor smoking history on recipient outcomes is controversial in the overall lung transplant population,
our findings suggest that the overall quality of HCV-viremic donor organs support their continued use even in the setting of donor smoking history. Observed differences in cause of death between HCV D + R– and HCV D–/R–were not significant, but the low number of deaths among recipients of HCV D+/R– transplants indicates that ongoing monitoring is warranted.
We found that waitlist time was longer for HCV D+/R– recipients than for HCV D–/R– recipients. This contrasts with the shorter waitlist times for HCV D+/R– recipients reported in prior literature.
However, this likely reflects differences in measurement of waitlist time; we only had access to overall waitlist time, not waitlist time since decision to consider HCV D+ organ offers. Therefore, our findings likely indicate that patients who had been on the waitlist longer were more likely to consider HCV D+/R– transplants, particularly since the recipients of HCV D+/R– LT had longer waitlist times and lower LAS scores than recipients of HCV D–/R– LT. This is also consistent with interviews with HCV D+/R– lung transplant recipients that said they made the decision to broaden their donor acceptance criteria because of desperation and increasing symptom severity.
This might reflect a strategy of HCV D+ organ utilization for those likely to accrue more waitlist time before becoming critically ill enough to receive organ offers.
While broadening the donor pool should increase the number of transplants, there has been disagreement over the true impact of using HCV D+/R– transplants on national transplant volume. Models in Italy suggested a low rate of suitable lungs,
estimated an increase of 232 transplants, 132 fewer delistings due to health deterioration, and 50 fewer waitlist deaths during that 5-year period. This would have reduced waitlist times by 3% to 11%, depending on priority status.
the impact in the current era could be even greater. Evidence suggests that the interest in HCV D+ organ offers has increased despite concerns about stigma; Yuan and colleagues
found that DAAs have caused a 2.1-fold increase per year in waitlist candidate willingness to accept HCV D+/R– transplants. In addition, interviews of candidates who indicated willingness to accept an HCV D+/R– transplant reported they felt it would be very safe, regardless of the type of transplant they ended up receiving.
One of the greatest perceived obstacles to expanding the use of HCV D+/R– transplants is the availability and cost of DAAs. Several studies have found that the cost of these medications has been a barrier to insurance approval, with up to 95% requiring previous authorization and 24% to 35% requiring appeals to obtain insurance coverage.
Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting.
However, in both studies, insurance coverage was eventually obtained for all patients, and out-of-pocket cost was reduced to a median of $0-10 through patient assistance programs.
Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting.
Studies of the cost effectiveness of HCV D+/R– transplants in Australia identify significant cost savings per patient at multiple levels of DAA cost, suggesting a cost benefit in other health care systems.
However, studies of the cost-effectiveness of HCV D+/R– transplants in the United States are needed to aid advocacy efforts for insurance coverage of DAAs for HCV D+/R– transplant recipients. In addition, exploration of methods that shorten the necessary duration of DAA therapy, such as prophylaxis
Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients: an open-label nonrandomized trial.
Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.
the ethical permissibility of HCV D+/R– organ transplantation relies on access to posttransplant curative DAA therapy. The ongoing use of HCV D+/R– organ transplantation also requires close monitoring for any other postoperative effects of HCV-viremic organs—particularly when administration of DAAs is delayed to the outpatient setting—or administration of DAAs in this patient population whose pharmacotherapy is already complex.
An additional barrier to expanding the use of HCV D+/R– transplants might be center discomfort with the posttransplant care of these patients. At our center, we performed 15 HCV D+/R– transplants from 2019 to 2020; this represented 25% of our center's lung transplant volume in those years. Unadjusted 1-year survival is similar among recipients of HCV D+/R– and HCV D–/R– lung transplants (93.3% vs 91.9%). This is accomplished through a clear treatment protocol. Recipients of HCV D+/R– lung transplants receive a Transplant Infectious Disease consult, all Public Health Service Increased Risk Donor testing, and additional laboratory serologies, including a hepatitis C quantitative polymerase chain reaction test weekly for the first 12 weeks. A positive assay results in referral to the Transplant Infectious Disease service for testing (including HCV genotyping), management, and treatment. Treatment of viremia is prescribed by the transplant physician or transplant infectious disease specialist according to the most recent guidelines for a particular HCV genotype (see www.hcvguidelines.org). Lung transplant recipients with HCV viremia who remain inpatient past posttransplant day 14 will commence HCV treatment in the inpatient setting, whereas patients discharged by that time commence HCV treatment as outpatients. Monitoring while on HCV therapy includes monthly HCV polymerase chain reaction test and a comprehensive metabolic panel. An additional source of discomfort caring for these patients is concern about risk to health care personnel. However, recent data estimate this risk of infection transmission at 0.2% for those exposed to HCV antibody–positive blood through needlestick or sharps injury.
Our ability to study HCV D+/R– transplants in the United States was limited by the information available in the SRTR database, which might not include all variables considered by transplant centers, providers, and candidates when accepting an offer. Therefore, our evaluations of transplant decision-making must be made at the center and national levels. While these data include all lung transplants performed in the United States, the recent uptake of HCV D+/R– transplants results in a limited sample size and follow-up time with which to draw conclusions about the mid-term results of HCV D+/R– transplants. We therefore encourage ongoing evaluation of these outcomes as the number of transplants and duration of follow-up increase. Finally, the development of new medications and/or treatment regimens for HCV, which are ongoing, may affect the outcomes and cost of HCV D+/R– transplants and should be evaluated when sufficient data are available.
In conclusion, our findings underscore the mid-term safety of HCV D+/R– lung transplants and potential benefit of expanding the utilization of these donor lungs further. The growing evidence of the safety of HCV D+/R– lung transplants should be disseminated through educational campaigns to ensure maximum waitlist candidate access to these life-saving transplants.
Conflict of Interest Statement
The authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Appendix E1
Table E1Summary of results
Outcome
HCV D+/R– vs HCV D–/R– LT
Estimate
95% CI
P value
Posttransplant ECMO
aOR 1.94
0.89-4.22
.10
Prolonged ventilator support >48 h
aOR 0.68
0.52-0.89
.006
Tracheostomy
aOR 0.43
0.13-1.39
.16
Hospital length of stay
–3.8 d
–7.9-0.24
.07
Acute rejection
aOR 0.87
0.54-1.41
.58
Mortality
AHR
30 d
0.32
0.08-1.28
.11
1 y
0.80
0.52-1.22
.31
3 y
0.94
0.71-1.24
.66
All-cause graft failure
AHR
30 d
0.31
0.08-1.25
.10
1 y
0.80
0.53-1.22
.30
3 y
0.93
0.71-1.22
.59
All analyses were adjusted for donor age, sex, race, and smoking history; recipient age, sex, race, and LAS; and procedure (single vs bilateral lung transplant). HCV, Hepatitis C virus; HCV D+/R–, HCV-viremic donor and HCV-seronegative recipient; HCV D–/R–, donor and recipient both HCV-seronegative; LT, lung transplant; CI, confidence interval; ECMO, extracorporeal membrane oxygenation; aOR, adjusted odds ratio; aHR, adjusted hazard ratio; LAS, lung allocation score.
Table E2Multivariable Cox regression analysis of mortality risk among lung transplant recipients of hepatitis C-viremic versus hepatitis C-seronegative grafts, 2015-2020
Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation.
Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus-infected donors to noninfected recipients: an open-label nonrandomized trial.
Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.
Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting.
This work was supported by grant number F32-AG067642091A1 (Dr Ruck) from the National Institute of Aging (NIA) and K24-AI144954-08 (Dr Segev) from The National Institute of Allergy and Infectious Disease (NIAID). 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 US Government.
The data reported here have been supplied by the Hennepin Healthcare Research Institute 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 US Government.
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