HCV-infected Donors Research Articles

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.

Patient’s Perspectives of Experimental HCV-Positive to HCV-Negative Renal Transplantation: Report from a Single Site

Background: With growing transplant wait times, clinical trials are evaluating the safety and efficacy of transplanting HCV-infected donor (HCV+) organs into HCV-noninfected recipients (HCV D+/R-). Such transplants raise ethical questions about safety, consent, and access to organs. Methods: We interviewed eight of the ten total HCV D+/R- transplant recipients enrolled in a pilot clinical trial examining the safety and feasibility of these novel transplants regarding their experiences in the trial, including their decision-making and perceptions of the informed consent process. Results: All interviewees reported positive experiences and expressed confidence regarding their decision to participate. Participants accepted an HCV + organ based on their assessments of the risks and potential benefits of HCV D+/R- transplants. For many, the risks of HCV were minimal compared to the risks of not receiving a transplant. All participants recalled providing informed consent, reporting that the process was thorough and that all their questions were addressed. Participants did not regret receiving an HCV D+/R- transplant and did not report experiencing stigma. However, given their understanding of HCV cure rates in the general population and the survival benefit associated with kidney transplantation, participants may have conflated research regarding HCV D+/R- transplantation with clinical care, suggesting a potential therapeutic misconception. Conclusions: Recipients of experimental HCV D+/R- transplants generally seemed to recognize the risks and benefits of these novel transplants and did not regret participating. Such salutary reported experiences are important in assessing the appropriateness of further research into the feasibility of HCV D+/R- transplants.

Pre-emptive pangenotypic direct acting antiviral therapy in donor HCV-positive to recipient HCV-negative heart transplantation: an open-label study

Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts. Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov, number NCT03208244. 55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart-kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0-8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8-57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5-18·0). Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known. American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.

Use of HCV-infected organs in solid organ transplantation: An ethical challenge but plausible option.

Due to the unfortunate epidemic of opioid overdose deaths among people who inject drugs (PWID) in North America, there has been an increase in the availability of hepatitis C (HCV)-positive organs for transplantation and consequently the potential to decrease waiting times for solid organ transplantation if an HCV-uninfected recipient is willing to accept an HCV-positive donor. The confidence in this potential new strategy comes as a result of the advent of safe and highly effective pan-genotypic direct-acting antivirals (DAAs). This promising strategy has been the most widely studied in kidney transplantation. Liver transplantation has positive results preliminarily, but has even less available data because viable HCV-infected donor livers are typically transplanted into HCV-infected individuals. Further, while HCV-infected heart and lung transplantation, which face additional post-transplant issues, have shown encouraging results, these studies are small scale and are limited by short-term follow-up. Thus, it would be premature to implement this strategy as standard of care without large scale clinical and real-world trials and longer-term follow-up studies. Further, the ethics of this practice need to be considered. While some transplant professionals argue that more harm will be done by not utilizing HCV-infected organs, others contend that cautiously conducted multi-centre studies involving extensive post-transplant follow-up are paramount prior to endorsing widespread implementation of this strategy. The ethical permissibility of this practice hinges on whether access to DAA therapy can be secured in advance, and prospective recipients understand and accept all the risks associated with acquiring HCV.

Process of selecting and educating HCV-uninfected kidney waiting-list candidates for HCV-infected kidney transplantation.

Long waiting times for kidney transplant (KT) and the high risk of mortality on dialysis have prompted investigation into strategies to utilize hepatitis C virus (HCV)-infected organs to decrease discard rates of potentially viable kidneys. Due the opioid epidemic, the number of HCV-infected donors has increased significantly. With the development of direct-acting antiviral therapies for HCV infection, now more than 95% of patients who received treatment are cured. Experimental trials have used direct-acting antiviral therapy to treat HCV infection in HCV-uninfected transplant recipients of kidneys from HCV-viremic donors. To date, HCV has been eradicated in all cases. Though these strategies will potentially increase the donor pool of available kidneys, shorten waitlist times, and ultimately decrease mortality in patients waiting for KT, identifying the ideal candidates and educating them about a protocol to utilize direct-acting antiviral therapy to cure HCV after it is transmitted is essential. We present our approach to patient selection and education for a clinical trial in transplantation of HCV viremic kidneys into uninfected recipients.

Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients

BackgroundHearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection.MethodsWe conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir–velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation.ResultsA total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.ConclusionsIn patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.)

Evaluation of Early Allograft Function in Donor HCV-Positive to Recipient HCV-Negative Cardiac Transplantation Managed with Preemptive Direct Acting Antiviral Therapy

Purpose Donor availability has continued to be a major issue limiting the number of cardiac transplantations in the United States. Given this shortage, it is necessary to consider strategies aimed at increasing the donor pool. We sought to evaluate the expanded use of hepatitis C virus (HCV) donor hearts, and characterize early allograft function in HCV-negative patients receiving pre-emptive anti-viral therapy following receipt of an HCV-infected donor heart. Methods Patients who underwent heart transplantation with HCV-positive donors at our institution between November 2017 and October 2018 were studied. Invasive hemodynamic and echocardiographic data were collected from routine scheduled post-transplant procedures. Intensive care unit (ICU) time, time on inotropes and time until discharge were evaluated from the index hospitalization for heart transplantation and compared to data from our center in patients receiving non-HCV hearts between January 2016 and June 2018. Results In total, there have been 23 recipients of donor HCV-positive heart transplants. Cardiac allograft and patient survival has been 100% at a median of 114 (IQR 81-190) days post-transplant. The average time on inotropes was 4.7±3.3 days in recipients of donor HCV-positive heart transplants, average time spent in the ICU was 7.2±4 days in the study group compared with 7.8±7.8 days in patients receiving non-HCV hearts and the average time to discharge was 19 ± 9 days in the study group compared with 21±22 days in patients receiving non-HCV hearts (both p>0.05). Among 80 echocardiograms done on or after post-operative day 2 in recipients of HCV-positive donor hearts, the ejection fraction (EF) was 65±9% with a single value falling below 50% (45%) that normalized 6 days later. One and 8-week hemodynamic values, respectively, were as follows: right atrial pressure of 7±5 and 5±3 mmHg, mean pulmonary arterial pressure of 20±7 and 20±6 mmHg, mean pulmonary capillary wedge pressure of 14±6 and 11±5 mmHg, and cardiac index of 2.8±0.8 and 2.9±0.4 L/min/m2. Conclusion In this single-center prospective study, patients who received preemptive direct-acting antiviral therapy following receipt of an HCV-positive donor heart demonstrated preserved early allograft function post-transplant.

Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion

Availability of organs is a limiting factor for lung transplantation, leading to substantial mortality rates on the wait list. Use of organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), would increase organ donation, but these organs are generally not offered for transplantation due to a high risk of transmission. Here, we develop a method for treatment of HCV-infected human donor lungs that prevents HCV transmission. Physical viral clearance in combination with germicidal light-based therapies during normothermic ex-vivo Lung Perfusion (EVLP), a method for assessment and treatment of injured donor lungs, inactivates HCV virus in a short period of time. Such treatment is shown to be safe using a large animal EVLP-to-lung transplantation model. This strategy of treating viral infection in a donor organ during preservation could significantly increase the availability of organs for transplantation and encourages further clinical development.

Mortality and Kidney Transplantation Outcomes Among Hepatitis C Virus–Seropositive Maintenance Dialysis Patients: A Retrospective Cohort Study

Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. Retrospective cohort study. Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31,2014. HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. No data for HCV viral load or liver biopsy. HCV-seropositive patients experiencereduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

The viral safety of intravenous immune globulin

The viral safety of intravenous immune globulin (IVIG) preparations has been investigated since 1983 when it was discovered that non-A, non-B hepatitis (NANBH) could be transmitted by an experimental IVIG preparation. Recently, it has been demonstrated that the virus causing NANBH is the hepatitis C virus (HCV). A number of subsequent episodes of HCV transmission by IVIG have been reported, but not all the factors that have led to this transmission are clearly understood. However, based on two episodes of HCV transmission by anti-D immune globulin (formulated for intravenous administration), it appears that cold ethanol fractionation is important in ensuring viral safety because both of the implicated anti-D immune globulin preparations were manufactured without cold ethanol fractionation. Other HCV transmission episodes have been associated with chromatography (particularly DEAE-Sephadex chromatography) as a separation step carried out to further purify IgG, after cold ethanol fractionation, and it is possible that such a procedure has only a marginal partitioning capacity for infective HCV virions. The role of anti-HCV screening in improving the viral safety of IVIG preparations remains unclear, but a recent transmission episode by a previously safe IVIG preparation suggests that the absence of anti-HCV antibodies during plasma fractionation may affect the partitioning characteristics of HCV and may also cause a loss of neutralizing antibody against HCV. All of the IVIG preparations associated with HCV transmission have been formulated as freeze-dried preparations and this may have been important in stabilizing HCV during the period prior to administration to patients. No other viruses appear to have been transmitted by IVIG preparations, but prior to seroconversion, HCV-infected plasma donors may continue to contaminate plasma pools used for the manufacture of blood products, despite anti-HCV screening, and additional viral inactivation steps such as incubation at pH4 or solvent-detergent treatment should be incorporated into the production process of all IVIG preparations.

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.

Risks, benefits, and ethical questions associated with transplanting kidneys from hepatitis C virus-infected donors into hepatitis C virus-negative patients.

Utilization of kidneys from hepatitis C virus (HCV)-infected deceased donors has the potential to increase the number of kidney transplants by 500-1000 (or more) each year. This increase in the number of kidney transplants offers major opportunities to extend survival and improve quality of life for patients infected with HCV, as well as uninfected recipients. However, due to a lack of prospective safety and efficacy data on a sufficient number of HCV-negative recipients who received a kidney from a HCV-infected donor, as well as key logistical barriers, the practice of transplanting HCV-infected organs into uninfected recipients is not yet ready to be considered as standard of care. Ongoing research coupled with a collaboration between insurers and transplant centers might bring positive-into-negative transplant into the realm of standard of care in well-informed transplant candidates, regardless of HCV status.

Distribution of Hepatitis C Virus Genotypes and Related Risk Factors Among Iranian Blood Donors: A Penalized Logistic Regression

Background: The hepatitis C virus (HCV) is a blood born virus and the major cause of liver diseases worldwide. Distribution of HCV genotypes varies depending on geographical regions and routes of infection. Knowledge regarding the distribution of HCV genotypes and related risk factors plays an essential role in the control of HCV infection in the community. Objectives: The current study aimed at determining the current distribution of HCV genotypes and related risk factors among Iranian blood donors. Methods: In the current analytical, cross sectional study, 106 HCV-infected blood donors with detectable HCV RNA over the country were interviewed by trained physicians through a post-donation questionnaire on demographic, medical, and risk history from November 2015 to May 2017. The hepatitis C virus genotype was determined by sequencing of a segment of non-structural 5B region in HCV genome. Penalized logistic regression model was used for statistical analysis through STATA software. Results: Hepatitis C virus genotype was determined in all subjects, and the genotype 3a was the most frequent (65, 61.32%), followed by 1a (31, 29.25%), and 1b (10, 8.49%). Based on the multivariable analysis results, tattooing (adjusted odds ratio: 2.76; 95% confidence interval: 1.03 - 7.37) was associated with HCV genotype 3a. Conclusions: According to the results, it seems that changes in molecular epidemiology of HCV infection and replacement of HCV genotype 1a with 3a, characterized by an increase in genotype 3a and decrease in genotype 1a have occurred over the last decade among Iranian blood donors. Tattooing was an independent risk factor for HCV infection by genotype 3a.

Expanding deceased donor kidney transplantation

Due to the organ shortage, which prevents over 90 000 individuals in the United States from receiving life-saving transplants, the transplant community has begun to critically reevaluate whether organ sources that were previously considered too risky provide a survival benefit to waitlist candidates. Organs that many providers were previously unwilling to use for transplantation, including kidneys with a high Kidney Donor Profile Index or from increased risk donors who have risk factors for window period hepatitis C virus (HCV) and HIV infection, have been shown to provide a survival benefit to transplant waitlist candidates compared with remaining on dialysis. The development of direct-acting antivirals to cure HCV infection has enabled prospective trials on the transplantation of organs from HCV-infected donors into HCV-negative recipients, with promising preliminary results. Changes in legislation through the HIV Organ Policy Equity Act have legalized transplantations from HIV-positive deceased donors to HIV-positive recipients for the first time in the United States. Critical reexamination of deceased donor organs that were previously discarded has resulted in greater utilization of these organs, an increased number of deceased donor transplants, and the provision of life-saving treatment to more transplant waitlist candidates.

Use of hepatitis C viraemic organs in kidney transplantation: a need to hit the pause button?

Innovative solutions are needed to overcome the global disparity in patients awaiting kidney transplantation versus donor organs available. A new study reports a promising new strategy of transplanting kidneys from HCV-infected donors into HCV-uninfected recipients and treating their HCV with direct-acting antivirals post-transplant — recipients achieved HCV cure with excellent one-year kidney allograft function.

Update on Transmission Modes of Hepatitis C Virus Among Volunteer Iranian Blood Donors: Analysis of a Matched Case-Control Study by Penalized Conditional Logistic Regression

Background: Reducing the risk of transfusion transmitted infections (TTI) is one of the main concerns of blood transfusion systems. Evaluation of HCV risk factors in HCV infected blood donors is critical for donor selection and ensuring blood safety. The aim of this study was to evaluate known and putative risk factors of HCV infection in Iranian blood donors. Methods: This matched case-control study was conducted on serologically confirmed HCV positive blood donors (cases) and serologically negative HCV blood donors came back to Iranian Blood Transfusion centers over the country from November 2015 to May 2017. Cases and controls were matched by donation status and interviewed for demographic, medical, and risk histories. Penalized conditional logistic regression model with backward selection method was used in data analysis. STATA software version 13 was used for statistical analysis. Results: A total of 271 cases and 794 controls were interviewed. Age (AOR (5 year), 1.27; 1.13 - 1.42), intravenous drug abuse (AOR, 24.89; 10.2 - 60.82), religious self-flagellation (AOR, 7.02; 2.02 - 24.4), non-injecting drug abuse (AOR, 6.13; 2.49 - 15.13), history of blood transfusion (AOR, 5.22; 1.52 - 17.92), imprisonment (AOR, 4.81; 2.43 - 9.53), sharing personal razor (AOR, 4.55; 1.45 - 14.28), tattooing (AOR, 4.46; 2.37 - 8.38), extramarital sexual activity (AOR, 2.88; 1.40 - 5.87), cupping in outpatient place (AOR, 2.44; 1.08 - 5.52), tooth extraction (AOR, 2.35; 1.46 - 3.78), surgery (AOR, 1.98; 1.22 - 3.21), and intramuscular injection (AOR, 1.68; 1.06 - 2.68) found to be current independent risk factors for HCV infection demonstrated in 98.52% of cases. Conclusions: This is the first study to perform penalized conditional logistic regression model in data analyzing to control some statistical bias in the evaluation of HCV risk factors among Iranian blood donors. According to the results, intravenous drug abuse is a primary HCV risk factor. In addition, the study emphasizes on the role of other high-risk behaviors such as religious self-flagellation and high-risk procedures such as cupping in outpatient place in HCV transmission. Increasing donor education regarding HCV risk factors and more accurate donor selection needs to improve blood safety and protect recipients from potential HCV infection risk.

Transplantation of HCV-Infected Kidneys into Uninfected Patients

Recent pilot studies demonstrated cure of donor-derived hepatitis C virus (HCV) infection in seronegative recipients of HCV-infected donors (THINKER; N

Accepting hepatitis C virus-infected donor hearts for transplantation: Multistep consent, unrealized opportunity, and the Stanford experience.

The current mismatch between supply and demand of organs has prompted transplant clinicians to consider innovative solutions to broaden the donor pool. Advancements of direct-acting antiviral agent (DAA) therapy for hepatitis C virus (HCV) have allowed entertaining the use of viremic donor organs in nonviremic recipients. In this report, we describe the evolution of HCV treatment, ethics and informed consent, cost-effectiveness of HCV medications in treating acute HCV post-transplantation, and the Stanford experience with two HCV-viremic donor heart transplantations. We describe excellent short-term outcomes post-heart transplantation with HCV NAT-positive organs. The availability of this therapy may expand the donor pool. While we await larger-scale clinical data on the effectiveness and safety of DAA therapy in patients after heart transplantation, many transplant centers have already started accepting organs from HCV-infected donors, balancing the unknown long-term risks versus the benefits of shorter wait times and expansion of the donor pool. Protocols and multidisciplinary teams are needed to effectively communicate risk to potential recipients, to ensure timely DAA access, and to implement appropriate clinical follow-up in order to achieve excellent clinical outcomes and to maximize the donor pool by utilizing HCV-infected organs for heart transplantation.

Hepatitis C: Current Controversies and Future Potential in Solid Organ Transplantation.

To highlight the changing landscape of hepatitis C virus (HCV) infection in the context of organ transplantation. This focuses on areas of controversy and future potential in the era of highly effective direct-acting antiviral (DAA) agents. Since the advent of safe and highly effective DAA therapy, HCV infection is now curable in virtually all cases, including organ transplant recipients. Excellent drug tolerability and safety combined with high cure rates across all organ groups means that HCV is no longer a barrier to transplantation or its outcomes. Mounting data demonstrate the safety of using organs from HCV-infected donors with subsequent treatment of HCV in the recipient and a potential to expand the donor pool. Historical data demonstrating inferior survival in transplant recipients with HCV is of limited relevance in the DAA era. Virtually all transplant recipients with HCV infection can be cured, while early data also suggest excellent outcomes in recipients of organs from HCV viremic donors. The optimal timing of HCV therapy in relation to transplantation and the optimal use of organs from HCV viremic donors remain areas of controversy and ongoing research efforts.

Transplantation of hepatitis C virus infected kidneys into hepatitis C virus uninfected recipients.

Long wait times for kidney transplant and the high risk of mortality on dialysis have prompted investigation into strategies to increase organ allocation and decrease discard rates of potentially viable kidneys. Organs from hepatitis C virus (HCV) antibody positive donors are often rejected; nearly 500 HCV-infected kidneys are discarded annually in the United States. Due the opioid epidemic, the number of HCV-infected donors has increased because of a rise in both new HCV infections and drug-related deaths. In the past 5 years, HCV has been transformed into a curable illness with direct-acting antiviral therapies (DAAs) that are effective in >95% of patients treated and are extremely well tolerated. Recent data has shown several direct-acting antiviral combinations are safe and effective after kidney transplant, and can achieve the same high cure rate seen in the general population and without increasing the rate of acute rejection. Because of this, strategies to decrease discard of HCV-infected organs have been devised. Two recent studies have transplanted HCV-uninfected dialysis patients with kidneys from donors actively infected with HCV; recipients were treated with DAA in the peri-transplant period. More research is needed to determine the safety and efficacy of this approach, but it has the potential to dramatically increase the donor pool of available kidneys, shorten waitlist times and ultimately decreases mortality in patients waiting for kidney transplant.