Viremic Donors Research Articles

Should My Patient Accept a Kidney from a Hepatitis C Virus-Infected Donor?

The availability of direct-acting antiviral (DAA) agents that reliably offer cure rates exceeding 95% for patients with CKD and patients with ESKD infected with hepatitis C virus (HCV) (1) has had a significant effect on the retrieval and allocation of kidneys from HCV-infected donors. Presented with increasing numbers of kidney offers from viremic donors, the transplant community has studied the feasibility of using these kidneys in an effort to increase access to kidney transplantation. Many transplant centers are now routinely performing transplants from HCV-viremic donors into HCV-positive recipients and initiating DAA treatment early after transplantation with excellent outcomes (2,3). This approach has translated into shorter waitlist times, increased access to transplantation, and a potential decrease in long-term morbidity and mortality for this patient population (2⇓⇓–5). In the context of studies demonstrating the safety and efficacy of the DAAs in kidney recipients (2,3,6,7), there has been increased interest in transplanting kidneys from HCV-positive donors into uninfected recipients. Agreeing to accept a kidney from a Public Health Service increased risk, HCV-infected donor requires informed consent at the time of listing, and in this context, many patients are being presented with this option and often seek advice and recommendations from their nephrologist. Understanding the pertinent literature on this topic will enable the nephrologist to actively participate in this decision and offer valuable guidance. Following the discovery of HCV and the availability of an ELISA to identify anti-HCV antibody, many cases of transmission of HCV with kidney transplantation were reported (8,9). Adverse consequences of transmission at the time of transplantation with resulting de novo HCV infection in the setting of intense immunosuppression included an aggressive form of fibrosing cholestatic hepatitis (FCH) and an immune complex injury to the allograft resembling …

Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C–Viremic Donor to Uninfected Recipient Kidney Transplantation

IntroductionLong wait times for kidney transplants have prompted investigation into strategies to decrease the discarding of potentially viable organs. Recent reports suggest that kidneys from hepatitis C virus (HCV)−infected donors may be transplanted into HCV-naive donors followed by direct-acting antiviral therapy.MethodsThis was a pilot clinical trial to transplant kidneys from HCV-infected donors into HCV-naive recipients with preemptive use of elbasvir and grazoprevir for 12 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy. Secondary outcomes were safety, quality of life, and early viral kinetics.ResultsA total of 33 patients were screened, and 8 underwent kidney transplantation from a HCV-viremic donors from August 2017 to March 2019. The median donor kidney donor profile index was 31% (range, 29%−65%), and patients who underwent transplantation waited a median of 6.5 months (range, 1−19 months). None had detectable HCV viremia beyond 2 weeks post-transplantation, and all achieved sustained virologic response 12 weeks after therapy (SVR12). There were no study-related severe adverse events. One patient experienced early graft loss due to venous thrombosis, whereas the remaining 7 patients had excellent allograft function at 6 months.ConclusionPreemptive elbasvir and grazoprevir eliminated HCV infection in HCV-naive patients who received a kidney transplant from an HCV-infected donor.

The impact of hepatitis C viremic donor lung allograft characteristics on post-transplantation outcomes

There is a low utilization rate of donated donor lungs. Historically, transplantation of lungs from hepatitis C-viremic donors to hepatitis C (HCV) negative recipients was avoided due to concern for worse graft survival. In the past few years with the advent of direct acting antiviral (DAA) therapy, there are emerging data suggesting the safety and efficacy of transplanting thoracic organs from HCV-viremic donors. This study assessed the differences in donor characteristics and allograft-specific clinical features at the time of organ offer and investigated whether these variables differed in HCV-viremic versus HCV-negative donors and impacted recipient outcomes. We conducted a single-center, retrospective cohort study of adult patients who underwent a lung transplant at Brigham and Women's Hospital between March 2017 and October 2018. Patients were stratified based on their donor HCV status (HCV-viremic versus HCV-negative). Donor and allograft-specific characteristics and clinical features including chest imaging and bronchoscopy reports, respiratory cultures, and the donor's oxygenation as measured by the arterial partial pressure of oxygen (PaO2) were collected as well as recipient baseline characteristics and transplant outcomes. During the study period, 42 and 57 lung transplants were performed from HCV-viremic and HCV-negative donors, respectively. Donor age was similar in both cohorts. More HCV-viremic donors died from drug intoxication (71% versus 19%, P=0.0001) and had a history of cigarette use (83% versus 5%, P=0.0001) and drug use (76% versus 49%, P=0.007). There were differences in the baseline recipient characteristics including a lower median lung allocation score in the HCV-viremic cohort. The organ-specific clinical characteristics including the terminal PaO2, chest imaging and bronchoscopy findings, and evidence of pulmonary infection were similar between the two cohorts. The recipient outcomes overall were excellent and did not differ significantly in both cohorts in terms of graft and patient survival at 6 and 12 months. Despite a greater proportion of HCV-viremic donors being increased risk with a history of drug and cigarette use and having died as a result of drug intoxication, the quality of the HCV-viremic donor organs did not differ from the HCV-negative donor organs or impact graft and recipient survival. Due to an increasing number of transplants from increased risk donors and in order to develop safe and effective protocols to perform lung transplants from HCV-infected donors, further characterization of the donor and allograft-specific clinical features and longer-term recipient outcomes is greatly needed.

Hepatitis C donor viremic cardiac transplantation: A practical approach.

Patients with end-stage heart failure eligible for orthotopic heart transplantation (OHT) exceed the number of available donor organs. With highly effective hepatitis C virus (HCV) antiviral therapy now available, HCV+ organs are increasingly utilized. We seek to describe our experience with patients receiving HCV viremic organs as compared to non-HCV transplant recipients. Our center began utilizing HCV hearts in February 2018. We retrospectively reviewed baseline demographics, laboratory data and outcomes for those undergoing OHT with majority being from a viremic HCV donor. Twenty-three of 25 HCV recipients received hearts from NAT+ donors with 22 of 23 seroconverting within 7days. Fifteen recipients have completed HCV treatment, with the longest duration of follow-up being 13months. No differences in rates of rejection, hospitalizations or death were seen between non-HCV and HCV transplant patients. With the advent of available direct-acting antivirals (DAAs), viremic HCV hearts provide an opportunity to increase organ availability. Moreover, treatment for HCV in the setting of immunosuppression is well-tolerated and results in sustained viremic response. Viremic, discordant HCV OHT can be performed in a safe and effective manner utilizing a systematic, multidisciplinary approach without an effect on short-term outcomes.

Trends in utilization of deceased donor kidneys based on hepatitis C virus status and impact of public health service labeling on discard.

Kidneys from deceased donors infected with hepatitis C virus (HCV) are underutilized. Most HCV virus-infected donors are designated as Public Health Service increased donors (PHS-IR). Impact of PHS and HCV designations on discard is not well studied. We queried the UNOS data set for all deceased donor kidneys between January 2015 and December 2018. The final study cohort donors (n=38702) were stratified into three groups based on HCV antibody (Ab) and NAT status: (a) Ab-/NAT- (n=35861); (b) Ab+/NAT- (n=973); and (c) Ab±/NAT+ (n=1868). We analyzed utilization/discard rates of these organs, the impact of PHS-IR and HCV designations on discard using multivariable two-level hierarchical logistic regression models, forecasted number of HCV viremic donors/kidneys by 2023. During the study period, (a) the number of viremic donor kidneys increased 2 folds; (b) the multilevel mixed-effects logistic regression models showed that, overall, the PHS labeling (OR 1.20, CI 95% CI 1.15-1.29) and HCV designation (OR 2.29; 95% CI 2.15-2.43) were independently associated with increased risk of discard; (c) contrary to the general perception, PHS-IR kidneys across all HCV groups, compared to PHS-IR kidneys were more likely to be discarded; (d) we forecasted that the number of kidneys from HCV viremic donor kidneys might increase from 1376 in 2019 to 2092 in 2023. Hepatitis C virus viremic kidneys might represent 10%-15% of deceased donor organ pool soon with the current rate of the opioid epidemic. PHS labeling effect on discard requires further discussion of the utility of this classification.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N=15) and the posttrial validation (Group 2B; N=25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N=27), median donor viral load was 1.37E+06IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R-transplants.

87. Heart and Lung Transplants From HCV-Viremic Donors to Uninfected Patients: Longer-Term Follow-Up

BackgroundThe DONATE HCV Trial demonstrated that hearts and lungs can be safely transplanted from HCV-infected donors using a shortened, 4-week, pre-emptive course of direct-acting antivirals (DAA). The 6-month results from that study of 35 patients are encouraging, but longer-term data from a larger cohort are needed to better define the risk–benefit profile.MethodsWe conducted a single-center trial to transplant thoracic organs from HCV viremic donors, irrespective of HCV genotype, to HCV-uninfected adults. Sofosbuvir/velpatasvir, a pan-genotypic DAA, was pre-emptively administered for 4 weeks, beginning within hours of transplant. The primary outcome was a composite of HCV clearance and graft survival at 6 months post-transplant. Secondary outcomes included graft survival and mortality at 12 months and the occurrence of grade 3 or higher adverse events (AEs). This protocol is IRB approved and all participants provided written informed consent (NCT03086044).ResultsBetween March 2017 and March 2019, 57 participants were enrolled: 46 received lung and 11 received heart transplants. The median donor HCV viral load (VL) was 889,817 IU/mL (IQR 212,062–4,641,078). Of the 57 recipients, 53 (93%) had detectable HCV VL immediately after transplant, with median VL of 1,460 IU/mL (IQR 463–6,618). HCV VL became negative by about 2 weeks and subsequently remained undetectable in all participants. Forty-nine of 49 (100%) and 34 of 35 (97%) participants were alive with excellent graft function and an undetectable HCV VL at 6 months and 1-year post-transplant, respectively. No treatment-related serious AEs were identified. Outcomes between transplant recipients from HCV donors vs. non-HCV donors were similar, including the occurrence of renal failure, respiratory failure, and non-HCV infections.ConclusionIn patients who received thoracic organs from HCV viremic donors, a 4-week antiviral treatment course initiated within hours of transplant prevented the establishment of HCV infection. These data demonstrate that thoracic organs from HCV viremic donors can be transplanted safely with excellent graft and recipient survival at 12 months with a similar AE profile compared with transplant recipients who received thoracic organs from non-HCV donors. Two-year outcomes will be available in October 2019.Disclosures All Authors: No reported Disclosures.

Estimated impact of hepatitis C-positive lung donor utilization on US donor lung supply.

The availability of highly effective direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection has led to reports of safely transplanting HCV+ donor lungs into HCV- candidates. However, it remains unclear how the ability to use HCV+ donor lungs for lung transplant could affect the number of donor lungs available for transplant. Using Scientific Registry of Transplant Recipient data, we identified all deceased organ donors within the United States from March 1, 2015, to February 28, 2018, and stratified by HCV status. A donor prediction model for lung donation was derived and validated within HCV- donors and applied to HCV+ donors to estimate the number of acceptable HCV+ lung donors. Of 29481 eligible donors, 2054 (7.0%) were HCV+ donors with 82 HCV+ donors' lungs being used for transplant during the study period. The prediction model for donor lung donation (specificity 92.6%, sensitivity 65.6%) estimated 248 HCV+ donors (75 nonviremic, 173 viremic) were acceptable for lung transplant during the study period, suggesting that 166 acceptable HCV+ lung donors were discarded. The ability to transplant lungs from HCV+ organ donors would lead to an estimated nationwide increase of at least 55 donor lungs per year, including 44 from HCV viremic donors.

Outcomes of heart transplantation from hepatitis C virus-positive donors.

National data demonstrate that increasing opportunities exist for organ donation among hepatitis C virus (HCV)-infected individuals. We developed a clinical practice protocol for the acceptance of HCV+ organs for HCV- patients who underwent heart transplantation (HT) and retrospectively reviewed the outcomes at our institution. Inclusion criteria were as follows: all adult patients listed for HT. Exclusion criteria were as follows: pre-existing HIV or active hepatitis B viremia in the recipient/donor. We transplanted 21 patients from HCV+ donors. Nineteen were viremic donors, and 2 were non-viremic donors. The recipients included 18 patients who underwent HT alone, and 3 patients who underwent combined heart-kidney transplants. There was no HCV transmission from the non-viremic donors (n = 2). All 19 recipients of the viremic donors developed HCV infection (100% transmission). The median age of the viremic donors was 34 years (interquartile range 30-46), and 84.2% were considered US Public Health Service-increased risk. Induction immunosuppression consisted of anti-thymocyte globulin (7/21), basiliximab (7/21), or none (8/21). Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and prednisone. Post-operative Week 2 HCV viral load was not related to induction. Direct anti-viral agent (DAA) therapy for a 12-week course consisted of glecaprevir/pibrentasvir (14/19, 74%), sofosbuvir/velpatasvir (2/19, 11%), elbasvir/grazoprevir (2/19, 11%), and ledipasvir/sofosbuvir (1/19, 5%). All the patients on DAA therapy cleared viremia. The sustained virological response rate at 12 weeks in 18 evaluable patients was 100%. We report successful single-center experience using HCV+ organs for HT into HCV- recipients. We believe that there is utility in using such organs to expand the current donor pool. Further long-term follow-up is needed.

Infectivity and stability of hepatitis C virus in different perfusion solutions.

Owing to organ shortage, transplantation of organs from HCV (hepatitis C virus) viremic donors into HCV negative individuals is getting more and more accepted. However, transmission of HCV to the host is nearly universal. Until now it is unknown if preservation solutions (PS) might alter infectivity and stability of HCV in the transplant setting. Therefore, seven different preservation solutions (PS) with variable composition were tested in vitro for their direct anti- and proviral effects on HCV. In vitro grown HCV based on the JFH-1 isolate was used to characterize the effect of seven different PS on the HCV replication cycle including HCV attachment, entry, replication, and assembly. In addition, HCV stability in PS was tested. Overall, 6/7 PS enhanced HCV infectivity: IGL-1 increased HCV attachment and entry, UW Belzer and Perfadex boosted HCV entry. Production of novel viral particles was enhanced in HTK, UW Belzer, and IGL-1. In contrast, viral replication was significantly reduced in HTK solution while all other PS had no effect on HCV RNA replication. HCV was significantly more stable in HTK solution. Euro Collins was the only PS that did not support HCV infectivity in cell culture. None of the used PS showed cytotoxic effects. Our data indicate that HCV infectivity and stability is maintained by several PS.

Transplantation of HCV Viremic Livers into HCV Viremic Recipients Followed by Direct-acting Antiviral Therapy.

Background and Aims: Hepatitis C virus (HCV)-infected organs are underutilized. We aimed to assess the safety and efficacy of direct-acting antiviral agents (DAAs) therapy in HCV viremic patients who are transplanted with a liver from a HCV viremic donor.Methods: We conducted a retrospective study, including patients seen from July 2015 to April 2017. HCV viremic patients transplanted with a liver from a HCV viremic donor and subsequently treated with DAAs were included. Outcomes assessed included undetectable viral load at 12 weeks after completing DAA therapy (sustained virologic response, SVR12), adverse events, and interactions with immunosuppression.Results: Twenty-four HCV viremic recipients received livers from HCV viremic donors. Median age was 63 years, and the majority (79.2%) were genotype 1a. Donors and recipients were viremic at the time of transplant. Median modified model for end-stage liver disease score was 19, and median time on the waitlist was 81 days. Median time from transplant to initiation of DAA therapy was 123 days. Several DAA regimens were used and 15 (62.5%) patients did not receive ribavirin. Treatment duration ranged from 12 to 24 weeks. Twenty-three (95.8%) patients achieved SVR12. Five (20.8%) patients developed adverse events; however, none required DAA discontinuation.Conclusions: DAA therapy was efficacious and well tolerated in HCV viremic recipients who underwent liver transplantation from a HCV viremic donor.

Balancing the risk and rewards of utilizing organs from hepatitis C viremic donors.

Owing to long waitlist times and high waitlist morbidity and mortality, strategies to increase utilization of hepatitis C viremic-deceased donor organs are under investigation in kidney, liver, heart, and lung transplantation. Direct-acting antiviral medications for hepatitis C virus infection have high cure rates and are well tolerated. Small, single-center trials in kidney and heart transplant recipients have demonstrated that with early posttransplant direct-acting antiviral therapy, 100% of uninfected recipients of hepatitis C viremic organs have been cured of infection after transplantation. In this manuscript, we review the risks and rewards of utilizing hepatitis C viremic organs for transplantation.

Increasing Utilization and Excellent Initial Outcomes Following Liver Transplant of Hepatitis C Virus (HCV)‐Viremic Donors Into HCV‐Negative Recipients: Outcomes Following Liver Transplant of HCV‐Viremic Donors

Direct-acting antiviral (DAA) therapy has altered the frequency and outcome of liver transplantation (LT) for hepatitis C virus (HCV). The high efficacy and tolerability of DAA therapy has also created a rationale for utilizing HCV-viremic (HCV-RNA-positive) donors, including into HCV-negative recipients. We examined trends in frequency of organ utilization and graft survival in recipients of HCV-viremic donors (HCV-RNA positive as measured by nucleic acid testing [NAT]). Data were collected from the Scientific Registry of Transplant Recipients (SRTR) on adult patients who underwent a primary, single-organ, deceased donor LT from January 1, 2008 to January 31, 2018. Outcomes of HCV-negative transplant recipients (R- ) who received an allograft from donors who were HCV-RNA positive (DNAT+ ) were compared to outcomes for R- patients who received organs from donors who were HCV-RNA negative (DNAT- ). There were 11,270 DNAT- /R- ; 4,748 DNAT- /R+ ; 87 DNAT+ /R- ; and 753 DNAT+ /R+ patients, with 2-year graft survival similar across all groups: DNAT- /R- 88%; DNAT- /R+ 88%; DNAT+ /R- 86%; and DNAT+ /R+ 90%. Additionally, there were 2,635 LTs using HCV antibody-positive donors (DAb+ ): 2,378 DAb+ /R+ and 257 DAb+ /R- . The annual number of DAb+ /R- transplants increased from seven in 2008 to 107 in 2017. In the post-DAA era, graft survival improved for all recipients, with 3-year survival of DAb+ /R- patients and DAb+ /R+ patients increasing to 88% from 79% and to 85% from 78%, respectively. Conclusion: The post-DAA era has seen increased utilization of HCV-viremic donor livers, including HCV-viremic livers into HCV-negative recipients. Early graft outcomes are similar to those of HCV-negative recipients. These results support utilization of HCV-viremic organs in selected recipients both with and without HCV infection.

Single Center Experience of Hepatitis C Donor Viremic Cardiac Transplantation

Purpose Patients with end-stage heart failure eligible for orthotopic heart transplantation (OHT) exceeds the number of available donor organs. With the introduction of curative medications for hepatitis C (HCV), these hearts are now being utilized in an effort to expand organ availability. The safety and feasibility of these organs in OHT has been previously described; however, many of the donor hearts were HCV immune and non-viremic. We seek to describe our experience with patients receiving HCV viremic organs. Methods St. Vincent Hospital in Indianapolis, IN began utilizing HCV hearts for OHT in February 2018. We retrospectively reviewed baseline demographics, laboratory data and outcomes for those undergoing OHT from a viremic donor. Results Basic information and results are reported in Tables 1 and 2. To date, 5 recipients have completed HCV treatment, with the longest duration of follow up currently 8 months. The average seroconversion time of a viremic heart was 7 days. Compared to non-HCV donors during this same timeframe, there was no increase in infection, rejection or number of hospitalizations. Additionally, patients completing antiviral treatment have had a sustained virologic response, with another 2 currently undergoing treatment and the final 3 awaiting insurance approval to initiate treatment. Conclusion In our early experience, we have demonstrated the feasibility of utilizing viremic HCV donor hearts for organ transplantation , thereby increasing the pool of available donors for patients that may not have otherwise received an organ. Further analysis of discordant HCV transplantation's financial impact is currently ongoing.

Outcomes of Heart and Heart-Kidney Transplantation from Hepatitis C Virus (HCV) Positive Donors into HCV Negative Recipients

Purpose Ongoing opioid epidemic has led to an increase in hepatitis C virus (HCV)+ organs. Given excellent cure rates with direct acting antivirals (DAAs), there is interest in using such organs for transplant. Methods We implemented a protocol to transplant HCV+ organs into HCV-recipients. This included patient/ provider education, 2-stage informed consent process, detailed donor/ recipient testing, and DAA therapy in the recipient. Inclusion criteria: All adult patients listed for heart transplant (HT). Exclusion criteria: Pre-existing human immunodeficiency virus or active hepatitis B viremia in the recipient/ donor. Results We transplanted 20 patients from HCV+ donors; 18 were viremic donors and 2 were non-viremic. Recipients included 17 HT alone and 3 combined heart-kidney transplants. There was no HCV transmission from non-viremic donors; all 18 recipients of viremic donors developed acute HCV infection. Among viremic donors, median age was 33.5 years, 89% were male, and 83% were PHS increased risk. Following HCV genotypes were noted: 1a (n=9), 1b (n=2), 2/2b (n=3), 3 (n=4) and 4 (n=1, concomitant 2b). Antiviral resistance testing was negative/indeterminate in all cases. Viremia was detected at day 3 in 69% (cut off >15 copies/ml) and week 1 in 87%. No recipient developed acute liver failure. Induction immunosuppression used: none (7/18, 39%), thymoglobulin (6/18, 33%), basiliximab (4/18, 22%), or both (1/18, 6%). Maintenance immunosuppression consisted of steroids, tacrolimus and mycophenolate mofetil as per center protocol. DAAs for 12-week course (one patient awaiting treatment): glecaprevir/pibrentasvir (13/17, 76%), sofosbuvir/velpatasvir (2/17, 12%), and elbasvir/grazoprevir (2/17, 12%). All patients on DAAs cleared viremia, sustained virological response rate at 12 weeks (SVR12) was 90% based on 10 evaluable patients (others need further follow-up; one died of un-related causes before SVR12 could be assessed). One patient developed cardiac allograft vasculopathy (from a non-viremic donor; none from viremic donors). Conclusion We report successful single-center experience utilizing HCV+ organs for heart/ heart-kidney transplantation into HCV-negative recipients. There is utility in using such organs in order to expand the current donor pool. Further long-term follow-up is needed.

Clinical Experience with Heart Transplantation from Hepatitis C Positive Donors

Purpose Advances in cure for active hepatitis C (HCV) have prompted consideration of HCV positive donors to address the continued shortage of organs. We have offered the option to accept HCV + donors, without any donor restrictions, to all patients on the waiting list. Methods From January to October 2018, 25 patients were transplanted, 12 patients from HCV viremic donors (NAT+). All recipients were seronegative at the time of transplantation. All patients were consented to receive an HCV donor as part of an IRB study. Survival and natural history of viral transmission and treatment were evaluated. Results 25 patients were transplanted with a mean age of 57 ± 12years, 28% females and 11 were blood type O (44%). All the recipients from HCV NAT + donors developed hep C viremia at 1-week postransplant. Therapy with glecaprevir/pibrentasvir (Mavyret) was initiated once seroconversion was established for duration of 8 weeks. All patients received standard triple immunotherapy. The HCV viremia cleared at a mean of 2.8 ± 2.1 weeks after initiation of therapy with a sustained viremic response at last follow up. There were no differences in early rejection rate or grade between patients receiving hearts from viremic versus non viremic donors. There were no significant abnormalities of liver function tests in patients with viremia. The shortest time on the waiting list was 3 days and the longest time was 197 days with a mean of 62 days. Eight recipients (32%) waited less than one month. At a mean follow up of 147 ± 88 days there was 100% graft and patient survival in both groups with no PGD. Conclusion While experience continues to grow, heart transplantation from donors with active hepatitis C is safe with excellent short term survival and rapid clearance of viremia. All patients develop viremia and respond to current antiviral therapy. These hearts represent an important potential resource from an underutilized donor pool and should be considered for transplantation. Long-term follow up is necessary.

Hepatitis and Thoracic Transplantation - No More Virus Non-Grata

Purpose There remains an urgent need to expand the donor pool for thoracic organ transplant recipients. Utilizing donors who are actively viremic with hepatitis C (HCV) is rapidly becoming standard practice, although no consensus exists regarding when to treat post-transplant, with which drug, and for how long. Cost remains an issue with direct acting antivirals (DAA). Hepatitis B (HBV) viremic donors are predicted to become more common. We designed and implemented a protocol to utilize HCV and HBV NAT+ donors. Methods We designed an open-label, ongoing safety and efficacy protocol to allow all transplant programs at our center, adult and pediatric, to enroll patients for whom there is an emergent need to expand the donor pool. Patients are consented and stratified into 2 groups: those who received NAT+ donors vs NAT- donor comparators. Patients are followed for a minimum of 12m post-transplant, with hepatitis viral loads measured at d5, 10 and 21 (and at clinical discretion thereafter). The primary end points are 3, 12month graft and patient survival. Secondary end points include viral cure rates, therapy associated adverse events, attributable hepatitis mortality, functional status, rejection rates and time to transplantation. HCV therapy of choice is started after discharge, or if needed urgently, begun inpatient and paid for by the hospital. HBV therapy is initiated at the time of transplantation. The protocol is monitored by a Data Safety Monitoring Board. Results 11 pts have enrolled to date and progressed to NAT+ transplant, including 8 adult heart transplants, 1 bilateral lung, 1 heart-lung and 1 lung-liver transplant. All have received HCV-viremic donors, within 1 month of consent. Median age is 56yrs (range 25-72). 3 recipients were HCV-viremic pre-transplant, 8 were HCV-naive. All 8 D+/R- pts became infected with HCV, 7 were actively viremic by day 5, one became viremic at d21. 9/9 patients are alive at 3months, with HCV therapy having been initiated in 6, and SVR12 achieved in 5 to date. So far we report 100% grafts survival, and no adverse events attributable to hepatitis. 1 patient required HCV therapy initiation in the hospital. Conclusion We present real world experience about the implementation of a protocol allowing HCV and HBV NAT+ donors to be used for thoracic and multivisceral transplants. Using a multidisciplinary approach, our protocol offers a means to expand the thoracic organ donor pool safely.

Magnitude of Recipient Viremia after Heart Transplantation from HCV Viremic Donors and Time to Clearance with Therapy

Purpose Due to advances in curative therapy for Hepatitis C infection, hearts from hepatitis C viremic (HCV) donors were successfully transplanted in selected patients. We assessed the relationship between the magnitude of recipient and time to HCV viremia clearance after transplantation. Methods From January until October 2018, 12 patients received heart transplantation from donors with active HCV viremia. All recipients developed viremia within one week and were treated with glecaprevir/pibrentasvir (Mavyret) for a duration of 8 weeks. HCV viral load was monitored weekly by real-time PCR . Results The mean age was 60 ± 8years, 33% were females, and 9 patients had non-ischemic cardiomyopathy (75%). All recipients (100%) had detectable HCV viremia at 1-week post heart transplant ; the lowest detectable viral load was 1. 36 log IU/ml and the highest was 7.06 log IU/ml, with a mean of 4.47 ± 2.13 log IU/ml (ref range 1.18 - 8 log IU/mL). Complete clearance of HCV viremia varied from 1 to 6 weeks with a mean of 2.8 ± 2.1 weeks. There was an association between the level of initial viremia and time to viral load clearance (Fig). At an average of 147 ± 88 days follow up, HCV viral load was undetectable in all patients. Forty percent of patients developed hepatitis C antibodies . There was no correlation between the level of initial viremia, duration of viremia clearance, genotype status and antibody response . Conclusion Heart transplantation from donors with active hepatitis C is safe with rapid clearance of viremia in all exposed patients. Time to viral clearance is related to initial viremic load. A sustained antibody response did not develop in all patients. This may be related to immunosuppression or relatively low level and duration of viremia.

The Impact of HCV Viremia in Heart Transplant Recipients from Donors with HCV Infection on Acute and Humoral Cellular Rejection

Purpose Transmission of HCV infection can induce an inflammatory response, but its impact on accentuating the immune response on the allograft is unknown. Methods From January to October 2018, 25 hepatitis C seronegative patients were transplanted with 12 patients from HCV viremic donors (NAT+). Incidence of acute cellular and humoral rejection were compared between the 2 groups. All patients received standard triple immunotherapy and those who developed HCV were treated with glecaprevir/pibrentasvir (Mavyret) for 8 weeks. Results For all patients, the retrospective flow cytometry crossmatch was negative for both T and B cells and no DSA were detected. Hep C viremia developed at 1-week post-transplant in all recipients of HCV donors. At a mean follow up of 147 ± 88 days in the HCV group: there were 4 grade 2R/ 3A rejection (33%) and 7 grade 1R/2 (58%). In the nonviremic group: there were 2 patients who had grade 2R/3A (20%) and 4 had grade 1R/2 (30%). No grade 3R or humoral rejection was identified in either group. Only grade 1R/2 rejection was statistically significant between the 2 groups. There was no difference in the type of inflammatory cells in the endomyocardial biopsy between the two groups. Conclusion Early biopsy of heart transplantation from donors with active hepatitis C is not associated with high grade cellular or any humoral rejection. The 1R/2A rejections seems to be more frequent in the HCV group and did not correlate with the level of viremia. Longer follow up and the impact on chronic allograft vasculopathy would need to be assessed in the future.

Lung Transplantation Using Hepatitis C Viremic Donors: An Open-Label Single Center Pilot Trial of Prevention of Viral Transmission

Background: A significant proportion of organ donors currently test positive for hepatitis C virus (HCV) infection. To date, only a few studies have evaluated the safety of using lungs from these donors for transplantation, and no direct interventions to donor organs have been performed with the aim of preventing HCV transmission via organ transplantation. Methods: We performed a single center prospective non-randomized trial where donor lungs from HCV viremic donors were transplanted into HCV negative (HCV-ve) recipients. Outcomes of study recipients were compared to patients receiving HCV-ve donors. Primary endpoints were survival and HCV status at 6 months after transplantation. Prior to implantation, all donor lungs were treated with ex vivo lung perfusion (EVLP) with (n=11) or without (n=11) ultraviolet C (UVC) perfusate irradiation to reduce HCV RNA levels and infectivity. All patients becoming viremic received 12 weeks of sofosbuvir/velpatasvir (S/V) starting at least 2 weeks after transplantation. Findings: During the 13-month study period, 22 patients were transplanted using viremic HCV donors and 187 with HCV-ve donors. Recipient age, lung disease, urgency status and positive donor-recipient HLA crossmatch were similar between the 2 groups. Post-transplant outcomes such as primary graft dysfunction grades, ICU and hospital length of stay, and survival were similar between the 2 groups. Twenty patients (91%) developed HCV viremia within the first week after transplantation and underwent S/V treatment starting at a median of 21 days after transplantation (range 14-71 days). Donor organ treatment with EVLP+UVC was associated with significantly lower recipient viral loads in blood within the first week after transplantation, and prevention of transmission in 2/11 patients. All infected patients achieved negative HCV PCR within 6 weeks of treatment initiation. Two patients presented with HCV relapse within 3 months after S/V completion requiring retreatment. Interpretation: Early and intermediate-term clinical outcomes using viremic HCV donors were similar to patients receiving HCV-ve donor lungs. Donor organ treatment using UVC perfusate irradiation during EVLP showed a significant impact in decreasing HCV viral loads within the first 7 days after transplantation. Trial Registration Number: The trial was registered at clinicaltrials.gov (NCT03112044). Funding Statement: This study was an investigator-initiated study funded by an operating grant from the Canadian Institutes of Health Research (CIHR). Gilead Sciences provided S/V (Epclusa) for all patients in the study. XVIVO perfusion (Gothenburg, Sweden) provided Steen solution for EVLP Declaration of Interests: Dr. Cypel, Waddell and Keshavjee are co-founders of Perfusix Canada, XOR Labs Toronto, and consultants for Lung Bioengineering (United Therapeutics). Ethics Approval Statement: This study was approved by the Research Ethics Board of University Health Network and subjects provided written informed consent while on the transplant waiting list prior to the offer of HCV+ve donor lungs.