HCV-viremic Organs Research Articles

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post-transplant viremia.

Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p=.43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p=.89, p=.87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p=.90, p=.88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p=6.7%vs. 12.8%, p=.3), acute cellular rejection (60.0%vs. 58.0%, p=.8) and antibody-mediated rejection (16.7%vs. 14.2%, p=.7). There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Using HCV-viremic organs for lung transplantation does not confer higher rejection rates compared to HCV-negative organs.

National data demonstrate that hepatitis C virus (HCV)-infected organ donors are increasingly being used in the US, including for lung transplantation. We aimed to assess whether there were any differences in the acute or chronic rejection rates at 1year following lung transplantation from HCV-viremic versus uninfected donors. We retrospectively reviewed all lung transplant recipients at our institution from April 1, 2017 to October 1, 2020 and then assessed various outcomes between those who received a transplant from HCV-viremic donors versus HCV-negative donors. Primary outcome was to determine if there was a higher incidence of acute and/or chronic allograft rejection when using HCV NAT+ lung donation. We carried out univariate and multivariate analyses. We transplanted 135 patients during the study period, including 18 from HCV-viremic donors. Standard induction therapy with basiliximab and maintenance triple drug immunosuppression was utilized per UC San Diego protocol. All 17 patients receiving HCV-viremic organs developed acute HCV infection and were treated in the postoperative period with 12weeks of direct acting antivirals (DAA). HCV genotypes included 1, 2, and 3. DAA used included glecaprevir/pibrentasvir (12), sofosbuvir/velpatasvir (1), and ledipasvir/sofosbuvir (2) with drug choice determined by patient's medical insurance coverage. Sustained virological response at 12weeks after end of DAA therapy (SVR12), indicative of a cure, was achieved in all (100%) recipients. No recipient had a serious adverse event related to HCV infection. The lung transplant recipient (LTR) HCV-viremic donors had lower rates of clinically significant rejection (5.9% vs. 11% LTR HCV-nonviremic donors), and no chronic lung allograft dysfunction at 1year (vs. 5.9% LTR HCV-nonviremic donors). One-year survival was 100% in the LTR HCV-viremic donors compared to 95.8% in the LTR HCV-nonviremic donors. We demonstrate the feasibility and success of using HCV NAT+donors with excellent results and without a higher incidence of rejection. Longer term follow-up and a larger sample size are needed to allow this to be a more widely accepted practice for lung transplant programs and payors.

Decision-making Among Hepatitis C Virus-negative Transplant Candidates Offered Organs from Donors with HCV Infection.

Background.Historically, many organs from deceased donors with hepatitis C virus (HCV) were discarded. The advent of highly curative direct-acting antiviral (DAA) therapies motivated transplant centers to conduct trials of transplanting HCV-viremic organs (nucleic acid amplification test positive) into HCV-negative recipients, followed by DAA treatment. However, the factors that influence candidates’ decisions regarding acceptance of transplant with HCV-viremic organs are not well understood.Methods.To explore patient-level perceptions, influences, and experiences that inform candidate decision-making regarding transplant with organs from HCV-viremic donors, we conducted a qualitative semistructured interview study embedded within 3 clinical trials investigating the safety and efficacy of transplanting lungs and kidneys from HCV-viremic donors into HCV-negative recipients. The study was conducted from June 2019 to March 2021.Results.Among 44 HCV-negative patients listed for organ transplant who were approached for enrollment in the applicable clinical trial, 3 approaches to decision-making emerged: positivist, risk analyses, and instinctual response. Perceptions of risk contributed to conceptualizations of factors influencing decisions. Moreover, most participants relied on multiple decision-making approaches, either simultaneously or sequentially.Conclusions.Understanding how different decisional models influence patients’ choices regarding transplant with organs from HCV-viremic donors may promote shared decision-making among transplant patients and providers.

HCV-Viremic Lung Transplantation Does Not Confer Higher Rejection Rates Compared to HCV-Negative Transplant

<h3>Purpose</h3> There is increasing utilization of hepatitis C virus (HCV)-infected organ donors for lung transplantation. Non-infectious outcomes are not clearly investigated in the literature. We aimed to assess acute and/or chronic rejection rates at one year following lung transplantation from HCV-infected donors. <h3>Methods</h3> After obtaining IRB approval, we retrospectively reviewed electronic medical records of patients that underwent lung transplant from 4/1/2017-10/1/2020 at our institution. Following data were abstracted - demographics, transplant details including surgery and immunosuppression, HCV management, outcomes including acute and chronic rejection as defined by ISHLT, and mortality. <h3>Results</h3> Among 76 patients transplanted during the study period, 15 received HCV-viremic allografts and 61 were from HCV-negative donors; details are noted in Table 1. Standard immunosuppression consisted of basiliximab induction followed by maintenance with tacrolimus, prednisone, and mycophenolate mofetil. We found no difference in the rate of acute or chronic rejection between the two groups. All 15 patients receiving HCV-viremic organs were treated with 12 weeks of DAA started at a median of 20 days (range 11-30) from surgery. The most prevalent genotype was 1/1a/1b (13/15, 84%). Most patients were treated with glecaprevir/pibrentasvir (12/15, 80%). All patients achieved sustained virological response at 12 weeks, indicative of a cure. There were no cases of HCV-related serious adverse events including fulminant hepatitis or death. Median lung allocation score at time of HCV+ transplant was 41 (IQR 34.6-62.6). <h3>Conclusion</h3> We report successful single-center experience using HCV-viremic organs for lung transplant with low rates of allograft rejection between the 2 groups though a small data set is a limitation. As experience using such organs for transplant continues to increase, longer term follow-up and multicenter data is needed.

Direct-Acting Antivirals and Organ Transplantation: Is There Anything We Can't Do?

The opioid epidemic has resulted in an increase in organ donors with hepatitis C virus (HCV) infection in the United States. With the development of direct-acting antiviral regimens that offer high sustained virologic response rates even in the setting of immunosuppression after transplantation, these HCV-viremic organs are now being offered to transplant candidates with or without preexisting HCV infection. Strategies for HCV treatment with HCV-viremic organs have included delayed and preemptive approaches. This review will discuss key studies in the different solid organ transplants, recent reports of adverse events, and ethical and regulatory considerations. The efficacy of current HCV therapies has created this important opportunity to improve survival for patients with end-organ failure through greater access to organ transplantation and decreased waitlist mortality rate.

Can HCV Viremic Organs Be Used in Liver Transplantation to HCV Negative Recipients?

Liver transplantation has steadily increased worldwide resulting in a large number of patients on the waiting list. Due to the opioid epidemic in the US, the pool of Hepatitis C seropositive donors increased significantly in recent years. Direct acting antivirals played an instrumental role in making liver transplantation with hepatitis C positive allograft an acceptable option. Although hepatitis C positive liver transplantation to hepatitis C positive recipients is a common practice, there is limited data and agreement on hepatitis C positive liver transplant to hepatitis C negative recipient. Thus, we review the current literature on this topic.

Hepatitis C Virus NAT-Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus-Negative Recipients: A Real-World Experience.

Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.

Rates of CAV are Not Elevated in Recipients of HCV Non-Viremic Organs

Recent data from single centers and registry analysis have demonstrated comparable one year survival after cardiac transplantation with HCV non-viremic donors. On the other hand, long-term outcomes remain unknown which is particularly relevant given the concern for accelerated CAV from HCV donors in the pre-DAART era. Therefore, in the current analysis we report our one year rates of CAV in recipients of HCV non-viremic organs. A retrospective chart review was conducted of all transplants at Montefiore Medical Center between January 2017 and April 2019. Recipients were divided into 2 cohorts based on donor HCV status: non-HCV or HCV non-viremic (Ab+/NAT-). Donor and recipient characteristics as well as presence of CAV at one year assessment were collected. CAV was defined as intimal thickness >0.5mm by IVUS or OCT of the LAD when available or in cases without IVUS/OCT as Grade 1 or greater per the 2010 ISHLT CAV recommendations. Patients who received a HCV viremic organ, died before one year or did not have one year CAV assessment were excluded. During the study period, 97 transplants were performed. Breakdown by HCV status was: 70 non-HCV, 21 non-viremic, and 6 viremic transplants. 48 subjects in the non-HCV and 14 in HCV non-viremic categories reached one year and underwent CAV assessment. Characteristics associated with the development of CAV including recipient age, donor age, pre-transplant PRA, and rejection in the first year were not statistically different between groups. Rates of CAV were not different between recipients of non-HCV and HCV viremic organs at one year: 27% vs 14% (p=.32). At the time of presentation we anticipate data on presence of CAV on all 97 patients. In this preliminary analysis, rates of CAV in recipients of HCV non-viremic organs were comparable to non-HCV donors. This finding provides further reassurance for the use of such donors in standard risk recipients.

Usage of HCV viremic organs in liver transplantation to anti-HCV negative recipients: The current status and review of literature.

Liver transplantation is the main curative therapy for end-stage liver disease. The number of transplanted organs is increasing globally. However, the number of available organs in the pool is insufficient, considering the excessive number of patients on the waiting list, which is a major concern for transplant programs. Hepatitis C infection (HCV) is a common indication for liver transplantation, and in recent years, a major progress has been made in its treatment with direct-acting antiviral (DAA) agents. HCV-positive livers have been transplanted to HCV-positive recipients for a long time. The high rate of sustained virologic response through DAA has brought new treatment options for the patients during the pre- and post-transplantation periods. Recently, there have been few reports of transplanting the available HCV-positive organs to HCV noninfected recipients. However, there is not yet an agreement on the optimal selection of patients who would benefit from such transplantation, and this has become a current topic of interest. Thus, we aim to review the current literature on this evolving topic.

Utilization rates and clinical outcomes of hepatitis C positive donor hearts in the contemporary era

Hepatitis C virus (HCV) donors should be categorized as HCV-viremic (antibody [Ab] negative or positive/Nucleic Acid testing [NAT] positive) or HCV Ab+nonviremic (Ab+/NAT-). Whereas recipients of hearts from HCV-viremic donors will develop viremia but can be cured of HCV shortly after transplant with direct-acting antivirals (DAAs), recipients of hearts from HCV Ab+ nonviremic donors are highly unlikely to become viremic or require DAAs. Given this important difference in risk, we assessed the utilization trends and post-heart-transplantation outcomes of HCV-naive (Ab-/NAT-), HCV-viremic, and HCV Ab+ nonviremic donor hearts. A total of 26,572 adult donors (≥18 years) with information on HCV Ab and NAT status were identified in the United Network for Organ Sharing registry between August 2015 and June 2018 for utilization rates. Adult heart transplant recipients of these donors were compared for primary graft failure (PGF) at 90 days and 1-year recipient survival. A total of 96 HCV Ab+ nonviremic and 135 HCV-viremic adult donor hearts were transplanted during the study period. The utilization rates of both HCV Ab+ nonviremic (1.4%-23.4%) and HCV-viremic (0.7%-25.4%) donor hearts increased significantly approaching HCV-naive rates (29.04%). There was no significant difference in rates of PGF and 1-year survival between recipients in the 3 donor HCV groups. We also used (1:3) propensity score matching and found similar 1-year survival in different donor HCV groups (HCV-naive vs HCV Ab+ nonviremic, p = 0.59, and HCV-naive vs HCV-viremic, p = 0.98). Recipients of HCV-viremic and HCV Ab+ nonviremic donor hearts had equivalent risk of PGF and 1-year mortality compared with recipients of HCV-naive donor hearts. Although only HCV-viremic organs require DAAs and the risk of coronary artery vasculopathy after treated HCV infection has not been defined, the utilization rates of both HCV Ab+ nonviremic and HCV-viremic adult donor hearts have increased at an equal pace now approaching HCV-naive rates.

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.

Center-level trends in utilization of HCV-exposed donors for HCV-uninfected kidney and liver transplant recipients in the United States.

Several single-center reports of using HCV-viremic organs for HCV-uninfected (HCV-) recipients were recently published. We sought to characterize national utilization of HCV-exposed donors for HCV- recipients (HCV D+/R-) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015-December 2, 2018) and Gini coefficients, we studied center-level clustering of 1193 HCV D+/R- KTs and LTs. HCV-viremic (NAT+) D+/R- KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV-aviremic (Ab+/NAT-) D+/R- KTs increased from<1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV- recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2-1.6) and 1.6 (0.4-3.5) years on the waitlist versus 1.8 (0.5-4.0) among HCV D-/R-. HCV- recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21-30) and 25 (21-32) at transplantation versus 29 (23-36) among HCV D-/R-. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R- transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R- transplants. There have been marked increases in HCV D+/R- transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R- transplantation.

Cost Effectiveness of Using Hepatitis C Virus (HCV)-Viremic Hearts for Transplantation into HCV-Negative Recipients

Purpose Direct acting antiviral (DAA) therapy has revolutionized the treatment of hepatitis C virus (HCV) infection with cure rates approaching 95-100%. There are recent reports of excellent outcomes following heart transplantation (HT) using HCV-viremic organs. Our aim was to assess the cost-effectiveness of using HCV-viremic hearts for transplantation into HCV-negative recipients with preemptive DAA therapy. Methods We developed a Markov model of disease progression among HCV-negative patients on the HT waitlist. We compared the cost-effectiveness between cohorts of patients willing to accept HCV-viremic or HCV-negative hearts and those only willing to accept HCV-negative hearts from a health care payer perspective with a lifetime time horizon. We examine cost-effectiveness for separate cohorts of waitlisted individuals on inotrope-dependent therapy (IDT) and with ventricular assist devices (VAD), incorporating transitions from IDT to VAD. We assumed 4.9% HCV-viremic prevalence among organ donors based on United Network for Organ Sharing (UNOS) data. We assumed all patients who received HCV-viremic hearts were treated with 12 weeks of DAAs with 95% primary and retreatment cure rates. Costs (in 2018 USD$) and health utilities (in quality-adjusted life-years) were attached to each stage and discounted 3%/year. Incremental cost-effectiveness ratios (difference in costs divided by the difference in QALYs) were calculated and considered cost-effective if falling below a $100,000 per QALY gained threshold. Results For both patient cohorts (VAD or IDT awaiting HT), accepting any heart (HCV-viremic or HCV-negative) was cost-saving compared to waiting for only HCV-negative hearts. For patients with a VAD awaiting HT, accepting any heart (HCV-viremic or HCV-negative) resulted in an increase in 0.1 QALY per patient, with an incremental cost of $-1151 compared to waiting for only HCV-negative hearts. For patients on IDT awaiting HT, accepting any heart (HCV-viremic or HCV-negative) was highly cost-saving (incremental costs $-32,971) due to averting potential costs of the VAD index hospitalization. Conclusion The use of HCV-viremic hearts for HCV-negative recipients is potentially cost-saving, and can improve clinical outcomes.

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.

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.