Viremic Donors Research Articles

Use of Hepatitis C Viremic Donors to Expand the Pediatric Donor Pool

The use of hepatitis C virus (HCV)-positive donors in organ transplantation has become increasingly viable due to advancements in direct-acting antiviral (DAA) therapies, which offer high cure rates. This review aims to evaluate the current practices, benefits, and challenges of utilizing HCV-positive donors for organ transplantation. The recent data show that transplant centers are progressively accepting HCV-positive donors for various organs, including kidneys, livers, and hearts, given the efficacy of post-transplant antiviral treatment. Using these donors has helped mitigate the organ shortage crisis, increasing the donor pool and reducing waitlist times. Despite these advantages, the approach raises concerns about viral transmission, long-term outcomes, and the cost-effectiveness of post-transplant DAA therapy. Furthermore, this review highlights the ethical implications of informed consent and the monitoring of HCV-negative recipients following transplantation. The outcomes from recent studies suggest that with proper management, transplantations from HCV-positive donors to HCV-negative recipients can be safe and effective, leading to excellent graft function and patient survival. This review synthesizes existing research and offers insights into optimizing protocols for future transplants involving HCV-positive donors.

Long-term outcomes of heart re-transplantation from HCV-viremic donors based on UNOS registry

Abstract Background The use of hepatitis C virus (HCV) viremic donors increased the heart donor pool, and reduced waitlist time and mortality among first-time single-organ heart transplant (HT) candidates without compromising their post-transplant survival. The outcomes of heart re-transplantation (re-HT) with the use of HCV-viremic donor grafts have not been investigated. Methods Using the United Network of Organ Sharing (UNOS) Registry we analyzed all adult patients who underwent single-organ heart re-HT in the United States between January 1, 2016, and December 31, 2022. HCV-viremic donors were defined by a positive nucleic acid amplification test (NAT+). Graft survival rates between HCV-viremic and HCV-non-viremic donor graft recipients were compared using a log rank test. Results During the study period, of 18,259 HTs performed, 427 (2.3%) constituted single-organ heart re-transplantations. Recipients of NAT+ grafts (n=19) compared to NAT- grafts (n=408) were more often male (84.2% vs 61.3%, p=0.04). Otherwise, there were no significant differences between the two groups in age, ethnicity, BMI, blood type, history of diabetes rates or stroke, creatinine or bilirubin levels, reason for re-HT, hemodynamics, use of mechanical circulatory support, and waitlist time. Ischemic time, frequency of female donors, HLA, ABO, CMV mismatch rates, and calculated panel reactive antibodies levels were comparable across the two groups. There were no significant differences in demographics or comorbidities rates between HCV-viremic and HCV-non-viremic donors apart from the cause of death. Among the donors of HCV-viremic grafts brain anoxia was reported more often (89.5%) than among HCV-non-viremic donors (40%), p <0.01. Rates of acute rejection treated in the first year after re-HT were comparable across the two groups. Over a mean follow-up of 3.0±2.1 and 3.3±1.8 years after re-HT from NAT- and NAT+ organ donors, respectively, graft survival rate at 1 year was 82% vs. 95% (p=0.3) and at 3 years 79% vs. 89%, respectively (p=0.6) (Figure). Conclusion Graft survival rates at 1 and 3 years post-heart re-HT in adult recipients of HCV-viremic donor grafts were comparable to those of recipients of HCV-non-viremic donor grafts. The current study provides compelling preliminary evidence that HCV-viremic donors constitute a viable donor pool for patients in need of heart re-transplantation.

Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States, 2020-2023

Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States, 2020-2023

Pathological Consequences in Anti-HCV Antibody-Positive Organ Donation to an Anti-HCV Antibody-Negative Recipient

BackgroundThe need to expand the pool of available organs has meant that the use of marginal organs is increasingly widespread. With the advent of antiviral therapy for hepatitis C, it has made it possible to consider the donation of organs from HCV positive donors or even from viremic donors. MethodsIn HCV positive to HCV negative antibody donor transplantation, the development of antibodies to HCV is documented unevenly depending on the organ transplanted and with differences in the time of appearance and in some cases with subsequent disappearance that draws attention to the fact whether it is the development of antibodies or the transmission of immunity between donor and recipient. In transplantation from HCV infected donor to negative recipient the introduction pre-transplantation or a few days after transplantation of antiviral therapy into the recipient achieves sustained response in almost all cases. We wanted to deepen the argument by studying the literature data, focusing on kidney transplantation, in consideration of the fact that this could be of interest in particular for the possible long-term renal damage. ResultsHCV infection both ongoing and past but also the presence of HCV antibodies alone can be responsible for kidney damage. ConclusionsDAA therapy has revolutionized the history of HCV disease and the therapeutic possibilities of transplantation. However, we believ it is useful to keep in mind the pathophysiology of HCV-related damage especially in patients with long life expectancy, using all emerging strategies to minimize the risk of transmission of infection or development of viremia.

The Spread Pattern of New Practice in Liver Transplantation in the United States.

Introducing new liver transplantation (LT) practices, like unconventional donor use, incurs higher costs, making evaluation of their prognostic justification crucial. This study reexamines the spread pattern of new LT practices and its prognosis across the United States. The study investigated the spread pattern of new practices using the UNOS database (2014-2023). Practices included LT for hepatitis B/C (HBV/HCV) nonviremic recipients with viremic donors, LT for COVID-19-positive recipients, and LT using onsite machine perfusion (OMP). One year post-LT patient and graft survival were also evaluated. LTs using HBV/HCV donors were common in the East, while LTs for COVID-19 recipients and those using OMP started predominantly in California, Arizona, Texas, and the Northeast. K-means cluster analysis identified three adoption groups: facilities with rapid, slow, and minimal adoption rates. Rapid adoption occurred mainly in high-volume centers, followed by a gradual increase in middle-volume centers, with little increase in low-volume centers. The current spread patterns did not significantly affect patient survival. Specifically, for LTs with HCV donors or COVID-19 recipients, patient and graft survivals in the rapid-increasing group was comparable to others. In LTs involving OMP, the rapid- or slow-increasing groups tended to have better patient survival (p=0.05) and significantly improved graft survival rates (p=0.02). Facilities adopting new practices often overlap across different practices. Our analysis revealed three distinct adoption groups across all practices, correlating the adoption aggressiveness with LT volume in centers. Aggressive adoption of new practices did not compromise patient and graft survivals, supporting the current strategy. Understanding historical trends could predict the rise in future LT cases with new practices, aiding in resource distribution.

Utilization of Hepatitis B viremic donors (NAT+) leads to improved kidney transplant access for older adult recipients with little to no wait time.

Though the use of Hepatitis B viremic (HBV) donor kidneys may be a safe alternative to improve access to transplantation, there has not been wide acceptance of this practice. In this study, we determined the safety and effectiveness of HBV NAT (+) donor kidneys in a protocolized manner in an older adult population. Over a 3-year period, 16 decreased donor kidney transplants were performed with HBV NAT+ kidneys. Recipients of HBV NAT+ kidneys were treated with entecavir started pre-operatively and continued for 52 weeks. HBV NAT+ kidneys were preferentially used in older (68 ± 5vs. 64 ± 9 years; p=.01) recipients with less dialysis time (93.8% < 5 years vs. 67% <5 years; p=.03). In this cohort, 3/16 had detectable HBV PCR 1-week post-transplant, but all were negative at 9- and 12-months. Calculated estimated glomerular filtration rate (eGFR) was slightly decreased 12-months post-transplant. Post-transplant outcomes in an age-matched cohort showed no difference in rates of delayed graft function, readmission within 30 days, and graft loss or death within 6 months of transplant (p>.05). Transplants with HBV NAT+ donor kidneys in a pre-emptive treatment protocol allow for increased safe access to transplantation in older adult recipients with little or no dialysis time.

(105) - Impact and Outcomes of Hepatitis C Viremic Donors (HCV-NAAT) on Donor-Derived Cell-Free DNA Levels and Gene-Expresion Profiling (GEP-Allomap) in Heart Transplant Recipients

(105) - Impact and Outcomes of Hepatitis C Viremic Donors (HCV-NAAT) on Donor-Derived Cell-Free DNA Levels and Gene-Expresion Profiling (GEP-Allomap) in Heart Transplant Recipients

(102) - Efficacy of Short Course Direct Acting Antivirals and Ezetimibe vs Longer Course of Direct Acting Antivirals to Prevent Hepatitis C Infection in Thoracic Transplant Recipients of Hepatitis C Viremic Donors

(102) - Efficacy of Short Course Direct Acting Antivirals and Ezetimibe vs Longer Course of Direct Acting Antivirals to Prevent Hepatitis C Infection in Thoracic Transplant Recipients of Hepatitis C Viremic Donors

(890) - Impact of Hepatitis C Viremic Lung Donors on Waitlist Time and Outcomes in High-Risk Recipients

(890) - Impact of Hepatitis C Viremic Lung Donors on Waitlist Time and Outcomes in High-Risk Recipients

(104) - Intermediate Term Outcomes of CAV Screening in Heart Transplant Recipients from Hepatitis C Viremic Donors versus Non-Hepatitis C Donors

(104) - Intermediate Term Outcomes of CAV Screening in Heart Transplant Recipients from Hepatitis C Viremic Donors versus Non-Hepatitis C Donors

Cardiac allograft vasculopathy in heart transplant recipients from hepatitis C viremic donors.

Recent studies suggest the transplantation of Hepatitis C (HCV) hearts from viremic donors is associated with comparable 1 year survival to nonviremic donors. Though HCV viremia is a known risk factor for accelerated atherosclerosis, data on cardiac allograft vasculopathy (CAV) outcomes are limited. We compared the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic acid amplification test positive; NAT+) compared to non-HCV infected donors (NAT-). We retrospectively reviewed annual coronary angiograms with intravascular ultrasound from April 2017 to August 2020 at two large cardiac transplant centers. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) ≥ 0.5mm was considered significant for subclinical disease. Among 270 heart transplant recipients (mean age 54; 77% male), 62 patients were transplanted from NAT+ donors. CAV ≥ grade 1 was present in 8.8% of the NAT+ versus 16.8% of the NAT- group at 1 year, 20%versus 28.8% at 2 years, and 33.3%versus 41.5% at 3 years. After adjusting for donor age, donor smoking history, recipient BMI, recipient, hypertension, and recipient diabetes, NAT+ status did not confer increased risk of CAV (HR.80; 95% CI.45-1.40, p=0.43) or subclinical IVUS disease (HR.87; 95% CI.58-1.30, p=0.49). Additionally, there was no difference in the presence of rapidly progressive lesions on IVUS. Our data show that NAT+ donors conferred no increased risk for early CAV or subclinical IVUS disease following transplantation in a cohort of heart transplant patients who were treated for HCV, suggesting the short-term safety of this strategy to maximize the pool of available donor hearts.

Hepatitis E Virus Infection in Voluntary Blood Donors in the Russian Federation.

Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were screened for HEV RNA using the cobas® HEV test in mini-pools of six plasma samples. Samples from each reactive pool were tested individually. The average HEV RNA prevalence was 0.024% (95% CI: 0.01-0.05%), or 1 case per 4081 donations. No statistically significant differences in HEV RNA prevalence were observed between the two study regions. The PCR threshold cycle (Ct) values ranged from 25.0 to 40.5 in reactive pools, and from 20.9 to 41.4 in reactive plasma samples when tested individually. The HEV viremic donors had different antibody patterns. Two donor samples were reactive for both anti-HEV IgM and IgG antibodies, one sample was reactive for anti-HEV IgM and negative for anti-HEV IgG, and two samples were seronegative. At follow-up testing 6 months later, on average, four donors available for follow-up had become negative for HEV RNA and positive for anti-HEV IgG. The HEV ORF2 sequence belonging to HEV-3 sub-genotype 3a was obtained from one donor sample. The sequencing failed in the other four samples from viremic donors, presumably due to the low viral load. In conclusion, the HEV RNA detection rate in blood donors in Russia corresponds with data from other European countries, including those that implemented universal donor HEV screening. These data support the implementation of HEV RNA donor screening to reduce the risk of transfusion-transmitted HEV infection in Russia.

Outcomes of Kidneys Transplanted From Hepatitis C Viremic Donors to Naive Recipients From an Appalachian Rural Kidney Transplant Program.

Before the advent of direct-acting antiviral therapy for hepatitis C virus, a large proportion of kidneys from donors with hepatitis C viremia were discarded. Hepatitis C virus is now amenable to effective treatment with excellent seronegativity rates. In this study, we review the outcomes of hepatitis C viremic kidneys transplanted into hepatitis C-naive recipients. In this retrospective observational study, we examined 6 deceased donor kidneys with hepatitis C viremia that were transplanted into hepatitis C-naive recipients between March 2020 and April 2021 at a single center. Because of health insurance constraints, patients were treated for hepatitis C virus with glecaprevir/pibrentasvir for 8 weeks following seroconversion posttransplant. Primary outcome measured was viral seroconversion; secondary outcomes included graft function, posttransplant complications, and all-cause mortality. On average, patients seroconverted 6 days (range, 4-10 d) after transplant and began treatment 26 days (range, 15-37 d) after seroconversion. An 8-week course of antiviral treatment was successful in preventing acute hepatitis C virus infection in all patients. Posttransplant median creatinine was 1.96 mg/dL (range, 1-4.55 mg/dL), whereas median estimated glomerular filtration rate was 41.33 mL/min/1.73 m2 (range, 17-85 mL/min/1.73 m2). Patient survival rate was 66.7%, and death-censored graft survival rate was 100%. Two patients died from unrelated reasons: 1 from acute respiratory failure secondary to SARS-CoV-2 infection and 1 from posttransplant lymphoproliferative disorder. Two patients developed allograft rejection posttransplant (1 developed antibody mediated rejection, 1 developed borderline T-cell-mediated cellular rejection). Other major complications included neutropenia, fungal rash, SARS-CoV-2 infection, cytomegalovirus, BK virus, and Epstein-Barr virus reactivation. Use of hepatitis C-viremic donor kidneys for transplant is a safe option and has great potential to increase the kidney donor pool, as long as high index of suspicion is maintained for allograft rejection and opportunistic infections.

Impact of Recipient Hepatitis C Virus (HCV) Sero-Status on the Outcomes Following Kidney Transplantation from HCV Viremic Donors in the Era of Directly Acting Anti-HCV Agent Use

Impact of Recipient Hepatitis C Virus (HCV) Sero-Status on the Outcomes Following Kidney Transplantation from HCV Viremic Donors in the Era of Directly Acting Anti-HCV Agent Use

Assessing Tissue Transmission of Hepatitis C Virus From Viremic Donor to Seronegative Kidney Transplant Recipients: A Case Series.

The transmission of hepatitis C virus from viremic donors to seronegative recipients of kidney transplantation is well documented. Pre-transplant administration of direct-acting antivirals prevents viremia, but the seroconversion rate is high. We studied the transmission of the virus through the transplanted tissue by determining viral RNA in 15 kidneys from 8 deceased viremic donors, 5 males and 3 females aged 52.3 ± 15years. HIV positive donors and active intravenous drugs abusers were discarded to avoid possible window periods in the virus transmission. Recipients, 9 males and 6 females aged 52.7 ± 18years, were treated with glecaprevir/pibrentasvir for 8weeks and received immunosuppression with thymoglobulin, tacrolimus, sirolimus and prednisone. Hepatitis C Virus was detected in 9 of the 15 histological samples analyzed but viremia was detected in no recipient at day 1 and 7 post-transplantation and 12weeks after the treatment. However, 13 of the 15 recipients had seroconverted within 1month. In conclusion, Hepatitis C virus was detected in a significant proportion of tissue of kidney grafts from viremic donors, but treatment with direct-acting antivirals avoids the transmission of the virus from donor to recipient. Then Donor pools should be expanded.

(855) Coronary Artery and Microvascular Physiology in Heart Transplant Recipients from Hepatitis C Viremic Donors

(855) Coronary Artery and Microvascular Physiology in Heart Transplant Recipients from Hepatitis C Viremic Donors

Outcome of Kidney Transplants from Viremic and Non-Viremic Hepatitis C Virus Positive Donors into Negative Recipients: Results of the Spanish Registry.

Historically, donor infection with hepatitis-C virus (HCV) has been a barrier to kidney transplantation. However, in recent years, it has been reported that HCV positive kidney donors transplanted into HCV negative recipients offer acceptable mid-term results. However, acceptance of HCV donors, especially viremic, has not broadened in the clinical practice. This is an observational, multicenter, retrospective study including kidney transplants from HCV positive donors into negative recipients reported to the Spanish group from 2013 to 2021. Recipients from viremic donors received peri-transplant treatment with direct antiviral agents (DAA) for 8-12 weeks. We included 75 recipients from 44 HCV non-viremic donors and 41 from 25 HCV viremic donors. Primary non function, delayed graft function, acute rejection rate, renal function at the end of follow up, and patient and graft survival were not different between groups. Viral replication was not detected in recipients from non-viremic donors. Recipient treatment with DAA started pre-transplant avoids (n = 21) or attenuates (n = 5) viral replication but leads to non-different outcomes to post-transplant treatment with DAA (n = 15). HCV seroconversion was more frequent in recipients from viremic donors (73% vs. 16%, p < 0.001). One recipient of a viremic donor died due to hepatocellular carcinoma at 38 months. Donor HCV viremia seems not to be a risk factor for kidney transplant recipients receiving peri-transplant DAA, but continuous surveillance should be advised.

Kidney transplant from HCV viremic donors to HCV-negative recipients and risk for de novo donor specific antibodies and acute rejection.

Kidney transplantation from HCV-viremic donors into uninfected recipients is associated with excellent short-term outcomes. However, concerns regarding an increased risk for the development of de novo donor specific antibodies (DSA) and acute rejection have been raised in single center reports. A retrospective study of HCV-negative kidney-only transplant recipients between 2018 and 2020. Patients were grouped based on the donor HCV status into group 1; HCV-viremic donors, and group 2; HCV-negative donors. Inverse probability of treatment weighting (IPTW), with weights derived from the propensity score, were used to estimate the effect of donors' HCV-viremia on the recipients. The primary objective was to compare the 1-year incidence of de novo DSA. Secondary outcomes included group comparison of the incidence of biopsy proven acute rejection (BPAR), 1-year patient and allograft survival, and 1-year renal allograft function. A total of 71 patients were included in the HCV NAT+ group, and 440 in the HCV- negative group. One-year incidence of de novo DSA was higher in the HCV NAT+ group in the IPTW weighted analysis (19%vs. 9%, p=.02). In the unweighted analysis, BPAR occurred in 7% of recipients in the HCV NAT+ group, compared to 3% in the control group (p=.06). However, due to the low event rate in the in the IPTW weighted groups, a statistical significance test could not be performed. Average estimated GFR was higher in the HCV-viremic group at 3 months (61vs. 53ml/min/1.73m2 p=.002), but comparable at 6 (59vs. 56ml/min/1.73m2 , p=.31) and 12 months (60vs. 55ml/min/1.73m2 , p=.07). Patient and allograft survival were comparable between the two groups. Kidney transplant from HCV-viremic donors was associated with an increased risk for the development of post-transplant de novo DSA in the first year after transplantation, but no difference in patient and graft survival.

Long-term follow-up of acute and chronic rejection in heart transplant recipients from hepatitis C viremic (NAT+) donors

The long-term safety of heart transplants from hepatitis C viremic (NAT+) donors remains uncertain. We conducted a prospective study of all patients who underwent heart transplantation at our center from January 2018 through August 2020. Routine testing was performed to assess for donor-derived cell-free DNA, acute cellular rejection (ACR), antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV). Allograft dysfunction and mortality were also monitored. Seventy-five NAT- recipients and 32 NAT+ recipients were enrolled in the study. All NAT+ recipients developed viremia detected by PCR, were treated with glecaprevir/pibrentasvir at the time of viremia detection, and cleared the virus by 59 days post-transplant. Patients who underwent NAT testing starting on post-operative day 7 (NAT+ Group 1) had significantly higher viral loads and were viremic for a longer period compared with patients tested on post-operative day 1 (NAT+ Group 2). Through 3.5 years of follow-up, there were no statistically significant differences in timing, severity, or frequency of ACR in NAT+ recipients compared with the NAT- cohort, nor were there differences in noninvasive measures of graft injury, incidence or severity of CAV, graft dysfunction, or mortality. There were five episodes of AMR, all in the NAT- group. There were no statistically significant differences between Group 1 and Group 2 NAT+ cohorts. Overall, these findings underscore the safety of heart transplantation from NAT+ donors.

Review of Renal Transplantation of Hepatitis C Viremic Donor Organs into Aviremic Recipients

The treatment of hepatitis C virus (HCV) has undergone significant changes within the past decade. One of these changes is the ability to treat hepatitis C with direct-acting antiviral agents (DAA) that do not involve the use of interferon.