Hepatitis C Virus Recipients Research Articles

Utilization and outcomes of expanded criteria donors in adults with congenital heart disease

BackgroundUse of donation after circulatory death(DCD) and hepatitis C virus(HCV) positive donors in heart transplantation have increased the donor pool. Given poor waitlist outcomes in the adult congenital heart disease(ACHD) population, we investigated waitlist outcomes associated with willingness to consider DCD and HCV+ offers and post-transplant outcomes following HCV+ and DCD transplantation for these candidates. MethodsUsing the United Network for Organ Sharing database, we identified adult ACHD candidates and recipients listed or transplanted, respectively, between 01/01/2016-09/30/2023 for the HCV analysis and between 12/01/2019-09/30/2023 for the DCD analysis. Among candidates, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider HCV+ and DCD offers. Among recipients of HCV+ (vs. HCV-) and DCD (vs. brain death[DBD]) transplants, we compared perioperative outcomes and post-transplant survival. ResultsOf 1,436 ACHD candidates from 01/01/2016-09/30/2023, 37.0% were willing to consider HCV+ heart offers. Of 886 ACHD candidates from 12/01/2019-09/30/2023, 15.5% were willing to consider DCD offers. On adjusted analysis, willingness to consider HCV+ offers was associated with 84% increased likelihood of transplant, and willingness to consider DCD offers was associated with 56% increased likelihood of transplant. Of 904 transplants between 01/01/2016-09/30/2023, 6.4% utilized HCV+ donors, and of 540 transplants between 12/01/2019-09/30/2023, 6.9% utilized DCD donors. Recipients of HCV+ (vs. HCV-) and DCD (vs. DBD) heart transplants had similar likelihood of perioperative outcomes and 1-year survival. ConclusionsACHD candidates who were willing to consider HCV+ and DCD offers were more likely to be transplanted and had similar post-transplant outcomes compared to recipients of HCV- and DBD organs.

Hepatitis B transmission/reactivation associated with Hepatitis B core antibody and Hepatitis C nucleic acid testing positive organs: A report from the Organ Procurement and Transplantation Network Disease Transmission Advisory Committee.

Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

Analysis of hepatitis C virus-positive organs in liver transplantation.

The authors of this study note that in liver transplantation (LT), the survival rates of hepatitis C virus (HCV)-positive donors and HCV-negative receivers are comparable to those of HCV-negative donors and recipients. Direct-acting antiviral (DAA) therapies have nearly 100% effectiveness in treating HCV. Between 2006 and 2016, the percentages of HCV-positive patients on the waiting list and HCV-positive LT recipients fell by 8.2 percent and 7.6 percent, respectively. Records from April 1, 2014, in which the donor and receiver were both at least 18 years old and had a positive HCV status, were the only ones eligible for the study. The analysis for this study was restricted to the first transplant recorded for each patient using a data element that documented the number of prior transplants for each recipient, although some recipients appeared multiple times in the data set. HCV-positive recipients or people with fulminant hepatic failure were the main beneficiaries of primary biliary cirrhosis among HCV-positive donors. However, there is still a reticence to use HCV-positive donor organs in HCV recipients due to clinical and ethical considerations. Similar survival rates between HCV-positive donors and recipients and HCV-negative donors and receivers illustrate the efficacy of these DAA regimens.

Donor and Recipient Hepatitis C Status Does Not Affect Rejection in Thoracic Transplantation

BackgroundDonors with hepatitis C virus (HCV) have expanded the donor pool for heart and lung transplantation, but concerns have arisen about rejection. We examined the incidence of rejection after heart and lung transplantation in recipients of HCV-positive donors as well as HCV-positive recipients. MethodsAdults undergoing heart and lung transplantation from March 31, 2015 to December 31, 2019 were identified in the United Network for Organ Sharing/Organ Transplantation and Procurement Network Standard Transplant Analysis and Research file. Patients were stratified as donor–recipient HCV negative, donor positive, and recipient positive. Comparative statistics and a multilevel logistic regression model were used. ResultsMeeting the criteria were 10 624 heart transplant recipients. Donor-positive recipients were significantly associated with older age, blood group O, and shorter waitlist time. No significant differences existed with regards to treatment for rejection in the first year (negative, 19.5%; donor positive, 22.3%; recipient positive, 19.5%; P = .45) or other outcomes. On regression analysis HCV status was not associated with treated rejection; however center variability was significantly associated with treated rejection (median odds ratio, 2.18). Similarly, 9917 lung transplant recipients were identified. Donor-positive recipients were more commonly White and had obstructive disease and lower lung allocation scores. Both unadjusted (negative, 22.1%; donor positive, 23.0%; recipient positive, 18.6%; P = .43) and adjusted analyses failed to demonstrate a significant association between HCV status and treatment for rejection, whereas center variability remained significantly associated with treatment for rejection (median odds ratio, 2.41). ConclusionsUse of HCV donors has expanded the donor pool for heart and lung transplantation. HCV donor status was not associated with treatment for rejection in the first year, but center variability played a role in the incidence and treatment of rejection.

Heart-Kidney Transplantation and Hepatitis C Virus Positive Donors

<h3>Purpose</h3> Novel hepatitis C virus (HCV) therapies have expanded the donor pool for heart transplantation (HT). However, multi-center data for heart-kidney transplant (HKT) recipients of HCV(+) donors is not yet available. <h3>Methods</h3> We analyzed adults undergoing first-time HKT between October 16^th, 2014 & December 31^st, 2019 using United Network for Organ Sharing (UNOS) registry; follow-up was available through March 4^th 2021. Data on recipient & donor characteristics were compared by donor's HCV status (defined as presence of either positive HCV antibody (Ab) or Nucleic Acid Test (NAT); Kaplan-Meier survival & Cox-proportional hazard estimates were computed. We also conducted a propensity score matching (PSM) analysis by matching HCV(+) donors with non-HCV donors. A separate sub-group analysis stratified by donor's HCV-Ab & NAT status was also performed. <h3>Results</h3> A total of 785 recipients (n=60 HCV(+) and n=725 non-HCV donors) were identified (age: 59 years (interquartile range (IQR): 51, 64), 82.4% males, 34.4% blacks). Recipients of HCV(+) donors were more likely to be from UNOS regions 1, 5, 10 or 11 & were transplanted at high-volume centers (p<0.05). HCV(+) donors were more likely to be older, Caucasians, smoker, dying of drug-overdose & with lower body-mass index (p<0.05). Distance between recipient & donor centers was significantly greater, resulting in longer ischemic times, & predicted heart-mass ratio was significantly lower among recipients with HCV(+) donors (p<0.05). Despite of these unfavorable factors, 1-year survival was similar between HCV(+) & non-HCV donors; similar trends were observed upon PSM analysis & sub-group analysis (<b>FIGURE</b>). Post-HKT length of stay (25 days (IQR: 14, 52) Vs 22 days (IQR: 15, 34), p=0.256) & index-hospital need for dialysis (32% Vs 33%, p=0.784) did not differ between recipients of HCV(+) and non-HCV donors, respectively. <h3>Conclusion</h3> Given excellent 1-year survival and short-term outcomes, HCV(+) donors offer an opportunity to expand the donor pool for recipients in need of HKT.

Outcomes of Adult Liver Retransplantation: A Canadian National Database Analysis.

Background Liver retransplantation remains as the only treatment for graft failure. This investigation aims to assess the incidence, post‐transplant outcomes, and risk factors in liver retransplantation recipients in Canada. Materials and Methods The Canadian Organ Replacement Register was used to obtain and analyse data on all adult liver retransplant recipients, matched donors, transplant-specific variables, and post‐transplant outcomes from January 2000 to December 2018. Results 377 (6.5%) patients underwent liver retransplantation. Autoimmune liver disease and hepatitis C virus (HCV) were the most common underlying diagnoses. Graft failure was 7.9% and 12.5%, and overall survival was 77.1% and 65.6% at 1 year and 5 years, respectively. In contrast to recipients receiving their first graft transplant, the retransplantation group had a significantly higher incidence of graft failure (p < 0.001) and lower overall survival (p < 0.001). The graft failure and patient survival rates were comparable between second transplant and repeat retransplant recipients. Furthermore, there were no differences in graft failure and patient survival when stratified according to time to retransplantation. Recipient and donor age (HR = 1.12, p=0.011; HR = 1.09, p=0.008), recipient HCV status (HR = 1.81, p=0.014), and donor cytomegalovirus status (HR = 4.10, p=0.006) were predictors of patient mortality. Conclusion This analysis of liver retransplantation demonstrates that this is a safe treatment for early and late graft failure. Furthermore, even in patients requiring more than two grafts, similar outcomes to initial retransplantation can be achieved with careful selection.

S1074 Evaluating Immediate Outcomes of Liver Transplantation With HCV Positive Donor Grafts

Introduction: Currently, there is a shortage of available deceased donors to meet the demands of the liver transplant (LT) waitlist, resulting in a mortality rate of 12.3 per 100 waiting list years in 20191. The advent of safe, effective treatment for hepatitis C virus (HCV) has permitted use of HCV infected grafts for LT. Here we performed a descriptive analysis comparing immediate transplant related outcomes in patients who received an HCV+ graft and those who did not. Methods: This is a single center prospective cohort study of patients listed for OLT from April 2018 - June 2020. We compared immediate transplant outcomes of (1) patients willing vs. unwilling to receive an HCV+ graft and (2) recipients of HCV+ liver (antibody or nucleic acid testing [NAT] positive) vs. all other LT recipients. Stata v14.0 software was used for descriptive statistics using Chi-squared testing for categorical variables and Kruskal-Wallis test for continuous variables. Results: 146 patients were enrolled in the study of which 111 underwent LT. 86 were willing to accept an HCV+ graft and 25 declined. 15 patients received a HCV+ graft, of which 10 were NAT positive. Among those willing to receive an HCV+ liver, there was no significant difference in patient or donor age. There was a trend toward decreased transplant wait time for patients willing to accept HCV+ livers (171 vs. 237 days; p=0.07). Patients who received an HCV+ graft had significantly shorter cold ischemic time (351 vs. 426 minutes, p=0.01) and a shorter hospital length of stay after LT (10 vs. 15 days, p=0.02). Between HCV+ vs HCV- liver recipients, there was no difference in recipient age, donor age, time to transplant, warm ischemic time, need for reoperation, post transplant diabetes, or place of disposition following LT. Conclusion: Our data demonstrates that patients who received an HCV+ graft had a shorter cold ischemic time and hospital length of stay after LT. The difference in cold ischemic time likely reflects the use of donors more local to the LT center. A shorter ischemic time might confer improved immediate allograft function which might explain the reduced hospitalization amongst our HCV+ liver recipient patients. The shorter length of stay after LT likely reflects patient selection and use of HCV+ organs in those with lower MELD score. Further work is needed to understand long-term outcomes following use of HCV+ grafts.

Clinical and Financial Implications of 2 Treatment Strategies for Donor-derived Hepatitis C Infections.

Background.Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays.Methods.At our institution, 2 strategies for providing DAA therapy to HCV– recipients of HCV+ transplants have been used. For thoracic organ recipients, an institution-subsidized course of initial therapy was provided to ensure an early treatment initiation date. For abdominal organ recipients, insurance approval for DAA coverage was sought once viremia developed, and treatment was initiated only once the insurance-authorized supply of drug was received. To evaluate the clinical impact of these 2 strategies, we retrospectively collected data pertaining to the timing of DAA initiation, duration of recipient viremia, and monetary costs incurred by patients and the institution for patients managed under these 2 DAA coverage strategies.Results.One hundred fifty-two transplants were performed using HCV viremic donor organs. Eighty-nine patients received DAA treatment without subsidy, and 62 received DAA treatment with subsidy. One patient who never developed viremia posttransplant received no treatment. Subsidizing the initial course enabled earlier treatment initiation (median, 4 d [interquartile range (IQR), 2–7] vs 10 [IQR, 8–13]; P < 0.001) and shorter duration of viremia (median, 16 d [IQR, 12–29] vs 36 [IQR, 30–47]; P < 0.001). Institutional costs averaged $9173 per subsidized patient and $168 per nonsubsidized patient. Three needlestick exposures occurred in caregivers of viremic patients.Conclusions.Recipients and their caregivers stand to benefit from earlier DAA treatment initiation; however, institutional costs to subsidize DAA therapy before insurance authorization are substantial. Insurance authorization processes for DAAs should be revised to accommodate this unique patient group.

Liver Transplantation Using Hepatitis C Virus-Viremic Donors Into Hepatitis C Virus-Aviremic Recipients as Standard of Care.

Liver transplantation (LT) using allografts from hepatitis C virus (HCV)‐viremic/nucleic acid testing–positive donors’ (DNAT+) organs into HCV‐aviremic recipients (rHCV−) has been limited owing to nearly universal HCV transmission and concerns regarding availability, safety, and efficacy post‐LT with direct‐acting antiviral (DAA) therapy. We report our experience of LT using DNAT+ organs into rHCV− as a routine standard of care. Following verification of DAA access, absence of critical drug‐drug interactions (DDIs) with DAAs, and informed consent, allocated DNAT+ organs were offered to patients on the waiting list for LT irrespective of recipient HCV status. Between June 2018 and December 2019, 292/339 rHCV− received an LT. Forty‐seven patients were excluded from analysis because of recipient HCV viremia, refusal to receive DNAT+ organs, or inability to receive DAA therapy post‐LT. Of these 292 patients, 61 rHCV− received DNAT+ livers (study group), and 231 rHCV− received DNAT− (aviremic donors [nuclear acid test‐negative donors]) livers (control group). Recipient and donor characteristics as well as 1‐year post‐LT patient and graft survival were similar between groups. In the study group, 4 patients died, and 1 patient required retransplantation within the first year post‐LT (all unrelated to HCV); 56 patients received DAA therapy, with a median time from LT to the start of DAA treatment of 66.9days (interquartile range [IQR], 36‐68.5), and 51 patients completed DAA treatment, all achieving sustained virologic response for 12 or more weeks (SVR‐12) (1 patient required retreatment owing to relapse following initial DAA therapy). No patients had evidence of fibrosing cholestatic hepatitis or extrahepatic manifestations of HCV. This report indicates that transplantation of DNAT+ livers into rHCV− and subsequent DAA therapy is associated with clinical outcomes comparable to those achieved with DNAT− allografts.

Transplantation of Kidneys From Hepatitis C Virus-Infected Donors to Hepatitis C Virus-Negative Recipients: One-Year Kidney Allograft Outcomes

Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. Retrospective cohort study. We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. Predictor(s) of donor infection with HCV. Kidney allograft function and allograft biopsy findings during the first year following transplantation. We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. Generalizability from a single-center study and small sample size was limited. Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.

Abstract 12659: Improved Heart Transplant Outcomes Among Patients With Hepatitis C Virus Infection in the Era of Direct-acting Antiviral Agents

Introduction: The effect of hepatitis C virus (HCV) infection in recipients or donors on heart transplants is less known in the era after the introduction of direct-acting antiviral agents (DAAs). Methods: Using the United Network for Organ Sharing registry, 25,581 adult heart transplant recipients between 2005 and 2019 were identified. The trend in prevalence of HCV infected recipients and in utilization of HCV infected donors and their effect on the transplant outcomes were investigated in the pre-DAAs era versus the DAAs era separated by May 13, 2011, using Cox proportional hazard regression. Results: HCV antibody positive recipients (n=532, 2.1%) had stable prevalence ( P =0.18) with a higher mortality risk in the pre-DAAs era (50.8% versus 38.8% at 10 years; hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.22-1.85; P &lt;0.001), however not in the DAAs era (25.3% versus 28.4% at 7 years; HR, 0.96; 95% CI, 0.72-1.28; P =0.79) ( P interaction&lt;0.001). Organ use from HCV antibody positive donors (n=375, 1.5%) was exclusively concentrated in the recent years ( P &lt;0.001) and provided the similar mortality up to 2 years (15.7% versus 12.4%; HR, 0.96; 95% CI, 0.65-1.43; P =0.84) regardless of the recipient HCV antibody status. The similar findings were confirmed with a subgroup cohort with positive nucleic acid amplification test (NAT). Conclusions: In the DAAs era, positive HCV antibody in recipients did not adversely affect the long-term transplant outcomes. Graft utilization from positive HCV antibody or NAT positive donors are rapidly more prevalent and appeared to be promising up to 2 years post-transplant.

State Medicaid Restrictions for Direct-Acting Antiviral Therapy Do Not Impact Posttransplant Outcomes of Recipients of Hepatitis C Virus-Viremic Livers.

The introduction of direct-acting antivirals (DAA's) has coincided with a rise in the number of deceased donors infected with hepatitis C virus (HCV). As a result, there has been increased utilization of livers from HCV-viremic donors, both for HCV-negative patients (including those previously treated for HCV) as well as HCV-positive patients whose treatment is delayed until after transplant. The use of DAA's has resulted in similar post-transplant outcomes in recipients of HCV-viremic vs HCV-negative donors, regardless of the recipient's HCV status.1.

Effect of Recipient Hepatitis C Status on Outcomes of Deceased Donor Kidney Transplantation

Hepatitis C virus (HCV) infection has been deemed detrimental to kidney transplantation (KT) outcomes. Breakthrough HCV treatment with direct-acting antiviral (DAA) medications improved the probability of HCV+ kidney use for KT even in noninfected (HCV-) recipients. We hypothesized that recipient HCV infection influences deceased donor KT outcomes, and this effect could be modified by donor HCV status and use of DAAs. We conducted a retrospective cohort study based on data from the Organ Procurement and Transplantation Network as of September 2018. A mate kidneys analysis was performed with HCV+ and HCV- recipients of solitary adult KT from ABO-compatible deceased donor between January 1994 and June 2018. We selected donors where 1 KT recipient was HCV+ and the mate kidney recipient was HCV-. Both HCV- and HCV+ donors were identified and analyzed separately. Outcomes, including survival of patients, grafts, and death-censored grafts, were compared between the groups. Four-hundred and twenty-five HCV+ and 5,575 HCV- donor mate kidneys were transplanted in HCV-discrepant recipients. HCV+ recipients of HCV- donor had worse patient and graft survival (adjusted hazard ratio 1.28; 95% CI, 1.19 to 1.37 and adjusted hazard ratio 1.26; 95% CI 1.18 to 1.34, respectively) and death-censored grafts (adjusted hazard ratio 1.24; 95% CI, 1.15 to 1.34) compared with HCV- recipients. Comparable patient and graft survival and death-censored grafts were found in recipients of HCV+ donors, regardless of recipient HCV status. The risk associated with HCV positivity in donors or recipients in the pre-DAA era (before December 2013) was no longer statistically significant in the post-DAA era. Given comparable outcomes between HCV+ and HCV- recipients in post-DAA era or when receiving HCV+ donor kidneys, broader use of HCV+ kidneys regardless of the recipient's HCV status should be advocated, and allocation algorithm for HCV+ kidneys should be revised.

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.

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.

Donor Small-Droplet Macrovesicular Steatosis Affects Liver Transplant Outcome in HCV-Negative Recipients.

Background No data are available on liver transplantation (LT) outcome and donor liver steatosis, classified as large droplet macrovesicular (Ld-MaS), small-droplet macrovesicular (Sd-MaS), and true microvesicular (MiS), taking into account the recipient Hepatitis C virus (HCV) status. Aim We investigate the impact of allograft steatosis reclassified according to the Brunt classification on early graft function and survival after LT. Methods We retrospectively reviewed 204 consecutive preischemia biopsies of grafts transplanted in our center during the period 2001-2011 according to recipient HCV status. Results The median follow-up after LT was 7.5 years (range: 0.0-16.7). In negative recipients (n=122), graft loss was independently associated with graft Sd-MaS, in multivariable Cox regression models comprehending only pre-/intraoperative variables (HR=1.03, 95%CI=1.01-1.05; P=0.003) and when including indexes of early postoperative graft function (HR=1.04, 95%CI=1.02-1.06; P=0.001). Graft Sd-MaS>15% showed a risk for graft loss > 2.5-folds in both the models. Graft Sd-MaS>15% was associated with reduced graft ATP content and, only in HCV- recipients, with higher early post-LT serum AST peaks. Conclusions In HCV-negative recipients, allografts with >15% Sd-MaS have significantly reduced graft survival and show low ATP and higher AST peaks in the immediate posttransplant period. Donors with >15% Sd-MaS have significantly higher BMI, longer ICU stays, and lower PaO2.

Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC, United States, 2014-2017.

We evaluated clinical outcomes among organ recipients with donor-derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014 to 2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti-HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti-HCV and HCV RNA. Donor risk behaviors were abstracted from next-of-kin interviews and medical records. During 2014-2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow-up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow-up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next-of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease, and death.

Characteristics and Short-Term Outcomes of Hepatitis C Antibody Positive Organs for Heart Transplantation: UNOS Analysis

Purpose Heart transplant centers are increasingly utilizing organs from donors infected with Hepatitis C virus (HCV). Aside from single-center experiences, there is little existing data regarding the characteristics of recipients of HCV Antibody (Ab)+ organs as well as short-term outcomes and graft survival. Methods We analyzed the United Network for Organ Sharing registry from January 2016 and March 2018 to include adults ≥18 who had undergone heart transplantation with a HCV Ab+ donor. Information regarding nucleic acid amplification testing (NAT) was also available. Results Between January 2016 and March 2018, 159 recipients underwent heart transplantation with HCV Ab+ donors. When comparing recipients of HCV+ to HCV- hearts, there were no differences between recipient age (53.4 vs 53.6 years, p =0.86), donor age (33.2 vs 31.9 years, p =0.055), female donor (26.0 vs 27.7%, p =0.64), body mass index (27.3 vs 27.6, p =0.47), and serum creatinine at transplant (1.4 vs 1.4, p = 0.36). There were no differences in the use of ventricular assist devices at time of transplant between groups. Recipients of HCV+ organs were more likely to be Blood Type O (55.3% vs 38.9%, p Conclusion While recipient baseline characteristics were similar between those receiving HCV+ and HCV- transplants, recipients of HCV+ organs had significantly longer ischemic times with longer distances from the donor hospital to the transplant center. Short-term survival appears similar between groups.

Estimated Impact of Hepatitis C Positive Lung Donor Utilization on US Donor Lung Supply

Purpose The advent of highly effective direct-acting antiviral agent (DAA) medications for hepatitis C virus (HCV) has led to reports of safe and acceptable short-term outcomes in recipients of HCV+ donor lungs. While further work is needed to establish the safety and optimal DAA protocols for transplanting HCV+ donor lungs, the potential impact of using HCV+ donor lungs to increase the donor lung supply within the United States is unclear. The aim of this study was to estimate the potential number of acceptable HCV lung donors within the United States. Methods All potential donors within the United States between March 1, 2015 and February 28, 2018 were identified from Scientific Registry of Transplant Recipients data and further classified by their HCV antibody and nucleic acid testing results into 4 categories: HCV-, HCV+ viremic, HCV+ non-viremic, and HCV undetermined. A prediction model of donor lung use within non-HCV positive donors was derived using conditional random forest methods and then applied to HCV+ donors. The number of observed and predicted HCV+ donors was calculated and further stratified by HCV viremia status and Organ Procurement and Transplantation Network (OPTN) region. Results There were 29,481 potential donors during the study period including 2,054 (7.0%) HCV+ donors (676 non-viremic and 1,378 viremic). HCV+ donors more frequently died from anoxia secondary to drug intoxication, had a greater frequency of cigarette use exceeding 20 pack/years, and had lower median lung PaO2 as compared to non-HCV donors. The lung donor prediction model had a sensitivity of 65.6% and a specificity of 92.6%. During the 3-year study period, there were 248 HCV+ lung donors (75 non-viremic and 173 viremic) estimated as acceptable for lung transplant as compared to an actual 82 HCV+ donors utilized for lung transplant. This translates to an estimated net increase of 166 transplants (55/year). The greatest increase was seen in OPTN regions 2, 3, 10, and 11. Conclusion This study estimates an annual increase of 55 lung transplants through the use of HCV+ lung donors. This is a conservative estimate given the high specificity but low sensitivity of the donor prediction model, and therefore the actual impact is likely greater. The potential impact varies by OPTN region and transplant centers within some regions are likely to see a greater impact from developing DAA protocols for HCV+ donor lung use.