HCV NAT Research Articles

Expanding the Deceased Donor Pool in Manitoba Using Hepatitis C-Viremic Donors: Program Report.

Purpose of program:The ongoing shortage of organs for transplant combined with Manitoba having the highest prevalence of end-stage renal disease (ESRD) in Canada has resulted in long wait times on the deceased donor waitlist. Therefore, the Transplant Manitoba Adult Kidney Program has ongoing quality improvement initiatives to expand the deceased donor pool. This clinical transplant protocol describes the use of prophylactic pan-genotypic direct-acting anti-viral agents (DAA) for transplanting hepatitis C (HCV)-viremic kidneys (HCV antibody positive/nucleic acid [nucleic acid amplification testing, NAT] positive) to HCV-naïve recipients as routine standard of care. We will evaluate the provincial implementation of this protocol as a prospective observational cohort study.Sources of information:Scoping literature review and key stakeholder engagement with interdisciplinary health care providers and health system leaders/decision markers.Methods:Patients will be screened pre-transplant for eligibility and undergo a multilevel education and consent process to participate in this expanded donor program. Incident adult HCV-naïve recipients of an HCV-viremic kidney transplant will be treated prophylactically with glecaprevir-pibrentasvir with the first dose administered on call to the operation. Glecaprevir-pibrentasvir will be used for 8 weeks with viral monitoring and hepatology follow-up. Primary outcomes are sustained virologic response (SVR) at 12 weeks and the tolerability of DAA therapy. Secondary outcomes within the first year post-transplant are patient and graft survival, graft function, biopsy-proven rejection, HCV transmission to recipient (HCV NAT positive), and HCV nonstructural protein 5A (NS5A) resistance. Safety outcomes within the first year post-transplant include fibrosing cholestatic hepatitis, acute liver failure, primary and secondary DAA treatment failure, HCV transmission to a recipient’s partner, elevated liver enzymes ≥2-fold, abnormal international normalized ratio (INR), angioedema, anaphylaxis, cirrhosis, and hepatocellular carcinoma.Key findings:This program successfully advocated for and obtained hospital formulary, provincial Exceptional Drug Status (EDS), and Non-Insured Health Benefits (NIHB) to provide prophylactic DAA therapy for this indication, and this information may be useful to other provincial transplant organizations seeking to establish an HCV-viremic kidney transplant program with prophylactic DAA drug coverage.Limitations:(1) Patient engagement was not undertaken during the program design phase, but patient-reported experience measures will be obtained for continuous quality improvement. (2) Only standard criteria donors (optimal kidney donor profile index [KDPI] ≤60) will be used. If this approach is safe and feasible, then higher KDPI donors may be included.Implications:The goal of this quality improvement project is to improve access to kidney transplantation for Manitobans. This program will provide prophylactic DAA therapy for HCV-viremic kidney transplant to HCV-naïve recipients as routine standard of care outside a clinical trial protocol. We anticipate this program will be a safe and effective way to expand kidney transplantation from a previously unutilized donor pool.

Management and tolerability of glecaprevir-pibrentasvir pharmacotherapy in hepatitis C viremic heart and lung transplant recipients.

We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose ratio (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (P=.79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient and discontinued in another due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.

Intermediate Survival Outcomes after Heart Transplantation Using Donor HCV NAT Positive Hearts

The availability of hepatitis C (HCV) antiviral therapy has made transplantation of HCV NAT+ donor hearts a new reality, expanding the pool of donor organs. We report the utilization and outcomes of transplantation of HCV NAT positive (HCV NAT+) hearts recorded in the United Network for Organ Sharing (UNOS) database. 11,252 heart transplant (HT) patients with HCV NAT status were reported by UNOS (2010-2019), of which 274 received an HCV NAT+ donor organ. Survival was evaluated at 24 months post HT. Demographics, comorbidities, hemodynamics were compared using standard statistical methods. Multivariate Cox-proportional hazard regression analysis (adjusted for age, sex, diabetes, ethnicity, ischemic time, dialysis, life support and HLA mismatch) was also performed for survival analysis. 274 patients received heart transplantation from HCV NAT+ donors. No significant difference in survival was identified at 24 months post-transplant (NAT + vs. -: 16.7% vs. 9.3%, p=0.70) despite longer allograft ischemic times in the HCV NAT+ group. HCV NAT+ recipients were older (Mean 53.6 ± 12.7 vs. 55.4 ±11.7 years, p=0.01) and also had older donors (Mean 32.1 ± 11.1 vs. 33.6 ± 8.1 years, p=0.02). Additionally, HCV NAT+ recipients had shorter median waitlist times (Median [inter-quartile range], 86.5 [18.0, 254.0] vs. 100.0 [29.0, 301.0], p=0.002). Multivariate analysis yielded a hazard ratio of 0.87 (CI 0.51-1.48) comparing NAT + to NAT - recipients. Intermediate survival post-transplantation is similar between HCV NAT+ and HCV NAT- recipients. Expansion of the donor pool via the inclusion of HCV NAT+ donors may shorten waitlist times and may extend donor organ availability.

Donor Derived Cell Free DNA in Recipients of Hepatitis C Viremic Donors as a Possible Marker of a Pro-Inflammatory State Causing Graft Injury

Since the highly effective Direct-Acting Antiviral (DAA) therapies have been available for treatment of HCV, transplant centers have begun using organs from HCV infected donors followed by treatment with DAAs. Epidemiological studies have shown that HCV may be associated with an increase atherosclerosis and it has been hypothesized that this is caused by activation of an immunological or inflammatory response. HCV infection of endothelial cells may promote endothelial dysfunction and early atherogenesis. The question arises, could acute HCV that is treated expeditiously, cause an inflammatory response leading to rejection or CAV in the heart transplant population. We plan to compare all recipients at our institution enrolled in the Surveillance HeartCare Outcomes Registry (S.H.O.R.E.) for increased donor derived cell free DNA (dd-cf DNA). They will be placed in 3 population categories: 1) Recipients of Non HCV donors, 2)Recipients of NAT positive donors and 3) Recipients of Antibody positive, NAT negative donors. After solid organ transplantation, donor-derived cell-free DNA circulates in the recipient's blood, and accounts for only a small fraction of total cfDNA (recipient plus donor-derived). During graft injury high amounts of donor-derived cell-free DNA (dd-cfDNA) are shed into the blood stream. HeartCare assesses heart health by measuring both immune activity and dd-cfDNA. The recommended threshold for Cell injury is greater than 0.2 % dd-cf DNA. We will compare populations by episodes of rejection, type of rejection and CAV at one year. At our institution there are currently 6 recipients of donor hearts that were HCV NAT positive and 3 recipients of HCV antibody positive but NAT negative. Participants will receive HeartCare at routinely scheduled intervals of every other month starting at month 4 for the first year and then quarterly out to 5 years post-transplant. We will compare populations by episodes of rejection, type of rejection and CAV at one year.

Use of Crushed Glecaprevir/Pibrentasvir in Hepatitis C Positive Donor Heart Transplant Recipients

Hepatitis C (HCV) positive donors have expanded the donor pool, though timing of initiation of direct acting anti-viral medications is highly variable across centers. A concern with using glecaprevir/pibrentasvir (GLE/PIB) de novo post transplant is administration in patients unable to swallow pills. We describe our experience with immediate post-transplant use of GLE/PIB in relation to sustained virologic response (SVR) based on route of administration. We analyzed all heart transplants from HCV donors to compare achievement of 12 week SVR in patients who swallowed GLE/PIB tablets to patients who had crushed GLE/PIB at any portion of their therapy. GLE/PIB started in recipients who received HCV NAT positive donor on call to the OR and continued for a total of 8 weeks. If patient was unable to swallow GLE/PIB was crushed and given via enteral tube. Of 76 heart or heart/kidney transplants were performed from 11/2017-5/2019, 26 received a HCV NAT positive donor and treated with GLE/PIB. One patient was excluded who died from sepsis 1 month post transplant despite 2 day HCV clearance and did not complete the course of GLE/PIB, leaving 25 for analysis. Eight patients (32%) received crushed GLE/PIB. Median duration of crushed GLE/PIB was 6 days. No difference was found in SVR or rapidity of clearance in patients who received crushed GLE/PIB. Initiation of GLE/PIB on call to the OR with administration via the oral or ng route post-operatively led to no difference in rapidity of HCV clearance and 100% SVR. Larger studies focusing on the details of drug absorption and kinetics are necessary to confirm these findings.

Incidence of Acute Cellular Rejection in Heart Transplant Recipients from Hepatitis C Viremic Donors – One-Year Follow-Up

Passive transmission of hepatitis C (HCV) viremia from actively infected donors to uninfected recipients at the time of heart transplantation may modulate response to alloantigens and risk of allograft rejection. We evaluated the one-year incidence of acute cellular rejection (ACR) in patients transplanted from nucleic amplification testing positive (NAT+) HCV donors compared to those from NAT negative (NAT-) donors. Since January 2018, 25 patients completed one-year follow-up. All recipients underwent right ventricular endomyocardial biopsy (EMB) per our institution protocol. ACR was graded according to both the 1990 and the revised 2004 International Society for Heart and Lung Transplantation (ISHLT) criteria. All NAT+ donor recipients developed viremia detected by RT-PCR. Mixed models were used to assess the association between donor HCV NAT status, recipient viremia, tacrolimus levels and ACR in the first year post-transplant. Twelve NAT+ recipients (mean age 60, 67% male) and 13 NAT- recipients (mean age 54, 77% male) completed one-year follow-up; 182 and 191 EMB were performed, respectively. NAT+ recipients were associated with higher grade rejection compared with NAT- recipients (p=0.041). At least one episode of high grade rejection (2R/3A) occurred in 4 NAT+ recipients (33%) compared with 2 NAT- recipients (15%). At least one episode of low grade rejection (1R/1B or 1R/2) occurred in 11 NAT+ recipients (92%) compared with 7 NAT- recipients (54%). These findings were independent of the presence and magnitude of viremia and tacrolimus levels. No episodes of ACR 3R or antibody mediated rejection were detected during one-year follow-up in either group. There was no allograft dysfunction or mortality related to ACR in either group. One year data from our institution demonstrate increased ACR in heart transplant recipients from NAT+ donors. Most of the rejection episodes in the NAT+ group were low grade and did not translate into any adverse outcomes through one-year follow-up.

Utilization of PHS Increased Risk for Transmission of Infectious Disease Donor Organs in Lung Transplantation: One Center's 7-year Experience

Over the past several years 37 to 41% of all deceased donor organs in Region 1 were designated as Public Health Service increased risk for infectious disease transmission compared to 25-27% nationally. Limited by the number of standard donors our Center sought to develop guidelines for utilizing these donors and implement a system for follow-up testing for disease transmission. We reviewed our single-center 7-year experience utilizing PHS donor organs in our lung transplant program. Our Center developed a protocol based on the PHS Guidelines to guide the lung transplant program in the management of recipients. Transplant recipients of PHS donor organs had blood testing (serology and viral load) for HIV, HBV and HCV performed on the day of transplant; 1-3 months and 6-12 months after transplant. A QAPI project was implemented to ensure medical record documentation and follow-up testing was conducted. From 2013 to October 2019 there were 66 lung transplants performed from PHS donor organs. A retrospective analysis revealed one false positive HIV antibody test; and 15 recipients (23%) converted their HBV core antibody from negative to positive at the 1-3 month time frame after surgery. Of the 15, 11 converted back to HBV core antibody negative within a year after transplant; 2 patients did not have testing performed/expired; and 2 patients were still within the first year after surgery and remained HBV core antibody positive. Although the etiology of the conversion remains unclear it was attributed to the administration of cytomegalovirus immune globulin in the recipients. Of note, 8 of the 66 PHS organs (12%) were also HCV positive and were transplanted under an IRB protocol. The recipients of HCV NAT positive donor organs were started on direct acting anti-viral agents. All of these patients remained HCV viral load negative after transplant. In addition to these donors, there was one HCV antibody/NAT positive donor organ that did not meet PHS criteria that was tracked and the recipient was HCV viral load negative after transplant. Our Center experience suggests that there is limited risk to using PHS donor organs in lung transplantation. Special considerations may be warranted in tracking recipients of HCV positive donor organs that may not meet PHS donor organ criteria.

Analysis of HCV RNA Genotypes and Quantitative Values of Korean HCV NAT Reactive Blood Donors

Analysis of HCV RNA Genotypes and Quantitative Values of Korean HCV NAT Reactive Blood Donors

New insights into the rational use of HCV+ organs worldwide.

Hepatitis C (HCV) is a worldwide health problem. Effective therapies for HCV infection, coupled with an increase in deceased donors due to the opioid epidemic, have led to the broader availability and the use of HCV-infected donor organs, including HCV nucleic acid test-positive (NAT+) donors in HCV-negative recipients. In this review, we discuss the prevalence of HCV infection, trends in the use of HCV-infected donors, and outcomes for those who receive HCV-seropositive or HCV NAT+ donor organs. We discuss management considerations such as hepatitis B reactivation, selection of the optimal direct-acting antiviral regimen, and potential complications. We also present a framework for the rational use of HCV-infected donor organs in the future.

Use of Donor HCV NAT Positive Hearts: Expanding the Donor Pool?

Purpose Use of HCV NAT+ donor hearts may aid in expanding the donor pool. However, limited single center data exist. We aim to assess the short-term impact of use of HCV NAT+ hearts in a national dataset. Methods 8256 HT patients with reported donor HCV NAT status were identified from UNOS (2010-2018), of which 88 received an HCV NAT positive (HCV+) donor. Exclusions included age proportional hazard regression analysis (adjusted for age, sex, diabetes , race, ischemic time , dialysis, life support & HLA mismatch) was performed. Results 88 pts underwent successful HT with HCV NAT positive donors. Predominant etiologies did not differ (p=0.169). During study period, 826 pts died post HT (NAT + vs -: 9.1 vs 10.0, p=0.77). Crude 1, 6 & 12 m post-HT survival was NAT+ [96, 91, 82%] vs NAT- [97, 93, 91%] (log-rank, p Multivariate analysis yielded a hazard ratio of 1.45 (CI 0.65-3.28) comparing NAT+ to NAT- recipients. Conclusion Short-term survival is similar between HCV NAT+ versus NAT- HT recipients. This data is promising and represents a step forward in expanding the donor pool. Further study is warranted to assess the long-term impact of this donor population.

Hepatitis and Thoracic Transplantation - No More Virus Non-Grata

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

Clinical Experience with Heart Transplantation from Hepatitis C Positive Donors

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

Characteristics of Hepatitis C+ vs Hepatitis C- Donors

Purpose With the advent of direct acting antiviral therapies (DAAs) for Hepatitis C (HCV), the use of HCV donors in adult heart transplantation is increasing. We sought to characterize HCV+ vs. HCV- donors to assess whether significant differences in donor quality and rates of organ acceptance and transplantation exist. Methods Between January 1, 2018 and August 15, 2018 we evaluated 427 heart transplant donors offered to the adult heart transplant program at Vanderbilt University Medical Center. We compared age, sex, BMI, cause of donor death, and rates of organ acceptance transplantation. We examined any heart donor during this time frame that was HCV antibody and/or HCV NAT positive. Results The Table demonstrates the characteristics of all 427 donors comparing HCV + vs HCV- donors. HCV+ donor hearts come predominantly from male donors among whom the overwhelming cause of death is drug overdose. These hearts have a higher likelihood of being accepted for transplant and being transplanted, relative to hearts from HCV- donors. Conclusion In the era of DAAs, utilization of HCV+ hearts is a viable strategy to help expand the donor pool.

Early experience with the use of hepatitis C antibody-positive, nucleic acid testing-negative donors in lung transplantation.

Historically, potential lung donors who have detectable antibodies to hepatitis C virus have been declined by most centers due to concern for possible disease transmission. We sought to evaluate hepatitis C viral transmission rates from donors who were known to be HCV Ab positive but HCV NAT negative. We performed a single-center retrospective review of a prospectively collected database for lung transplant recipients at our center including HCV Ab+NAT- donors (approved January 2017). Donor and recipient demographic data were compiled, and records were queried to ascertain rate of seroconversion. During the study period (1/1/17 to 8/9/17), a total of 64 recipients underwent lung transplantation. Thirteen (20%) donors were HCV Ab+NAT-. All recipients of HCV Ab+NAT- grafts were HCV Ab- at the time of transplant. Recipients of grafts from HCV Ab+NAT- donors underwent protocol NAT at 2 and 12months and all are NAT- to date. One recipient developed reactive HCV Ab at 6months post-transplant. Follow-up NAT showed HCV RNA to be undetectable. To date, use of HCV Ab+NAT- donors in lung transplantation has yielded favorable outcomes, with evidence of one transient seroconversion suggesting this practice may increase access to life-saving transplantation to those in need.

Increased Utilization of Hep C Donors With Concurrent Increase in Hep C Donor Pool

Introduction Both the number and proportion of HCV donors in this OPO’s service area increased significantly from 29 (6% of deceased donors) in 2013 to 83 (15% of deceased donors) in 2016. The HCV donor pool in the U.S. increased from 361 (4% of deceased donors) to 661 (7% of deceased donors) in the same time period. Methods This was a single OPO study. A retrospective analysis of utilization of kidneys, livers and hearts from HCV donors (HCV Ab+, HCV NAT+ or both) over 4 years was performed. Results The number of HCV donors procured increased by 186% from 29 in 2013 to 83 in 2016, while the overall donor pool increased by 20% from 447 to 540. The number of HCV kidneys, livers and hearts recovered for transplant increased by 180% from 68 to 190. Utilization of these organs increased by 51% from 47% in 2013 to 71% in 2016 despite the dramatic increase in the number of organs recovered from HCV donors. Conclusion OPOs should aggressively pursue HCV donors and transplant centers should consider utilization of HCV kidneys. Newly developed treatment protocols for HCV within this potential donor population should be evaluated to increase utilization of these kidneys in recipients without HCV.

The Practical Impact of Reactive HCV NAT and Anti-HCV Results

The Practical Impact of Reactive HCV NAT and Anti-HCV Results

Expanding access to transplantation with hepatitis C-positive donors: A new perspective on an old issue.

With the need for organs far exceeding supply, donors previously exposed to hepatitis B (HBV) and hepatitis C (HCV) viral infections should be considered for transplantation. Although many centers have protocols for transplanting organs from HBV core antibody-positive (HBcAb+) donors into select recipients, in the era of direct-acting antivirals (DAAs), a new focus should be placed on HCV-positive donors. The transmission rate from HCV antibody-positive (HCVAb+) nucleic acid testing negative (HCV NAT-) donors is expected to be very low, and we encourage use of such organs in HCV recipients provided a normal biopsy, appropriate counseling, and careful post-transplant monitoring. While transmission of HCV from HCV NAT+ donors is universal, the success of DAA in obtaining a sustained viral response in post-transplant recipients should make the use of these organs more appealing. We herein provide information to help guide the use of organs from HCV donors.

Priority needs and wisdom strategy for blood transfusion safety in developing low-resource countries

ObjectiveTo evaluate the implementation of alternative safety measures that reduce the risk of transfusion transmissible infections as an affordable measure in low resource countries. BackgroundIt is still difficult in developing countries with limited resources to mandate nucleic acid testing due to its high cost. Although NAT reduces the window period of infection, the developing countries are still in need of an efficient and effective transfusion programme before implementing the complex high cost NAT. Study Design and MethodsTwo thousand eight hundred eighty sero-negative first-time and repeat donations from Fayoum University Hospital blood bank were individually analysed by NAT for HIV, HBV and HCV. Only discriminatory-positive NAT were classified comparing the non-remunerated and family replacement donations. ResultsSignificant discriminatory-positive differences were observed for HBV NAT results, 2 remunerated donations compared to 0 non-remunerated sero-negative donations. The discriminatory positive differences were also significant for HCV NAT results, 4 remunerated donations compared to 1 non-remunerated sero-negative donation. No sero-negative, discriminatory-positive NAT HIV case was found. Seven out of 8 discriminatory positive cases were from first time donations. ConclusionIn order to ensure blood safety, the recruitment and retention of voluntary, non-remunerated repeat donors should be a major commitment for low resource countries in which NAT implementation is costly and not feasible.

Evaluation of Risk Minimisation Measures for Blood Components - Based on Reporting Rates of Transfusion-Transmitted Reactions (1997-2013)

Background: To assess the impact of safety measures, we compared reporting rates of transfusion-related reactions before and after the implementation of six measures in 1999, 2004, 2006, 2008 and 2009. Methods: Reporting rates of transfusion-transmitted bacterial infection (TTBI), viral infection (TTVI) and immune-mediated transfusion-related acute lung injury (TRALI) were calculated on the basis of confirmed annual reports and distributed blood components. Results: The introduction of HCV NAT testing caused a significant reduction of HCV reporting rate from 1:0.6 to 1:83.16 million administered blood components (p < 0.0001), donor screening for antibodies to hepatitis B core antigen caused a reduction of HBV reporting rate from 1:2.90 to 1:10.70 million units (p = 0.0168). A significant reduction from 1:0.094 to 1:2.42 million fresh frozen plasma (FFP) units could also be achieved by risk minimisation TRALI measures (p < 0.0001). Implementation of pre-donation sampling did not result in a significant decrease in TTBI, whereas limitation of shelf life for platelet concentrate (PC) minimised the TTBI reporting rate from 1:0.088 to 1:0.19 million PC units (p = 0.041). For HIV NAT pool testing, no significant reduction in HIV transmission was found due to very low reporting rates (1:10 million versus 1:27 million blood components, p = 0.422). Conclusion: On the basis of haemovigilance data, a significant benefit could be demonstrated for four of six implemented safety measures.

New approaches to in vitro diagnosis of hepatitis C infection a reason for post transfusion hepatitis: Diagnostic value of determination of hepatitis C virus core antigen

In between the dates of February 2008–March 2009, by applying to Istanbul University CTF Microbiology and Clinical Microbiology Basic Sciences Branch and Duzen laboratories, 123 cases, where HCV RNA and anti-HCV positivity are identified with molecular (real-time PCR) and serologic (ELISA) methods as a positive control group, and 48 cases where HCV RNA and anti-HCV negativity are identified as a negative control group are established. The values of sensitivity, specificity, positive and negative approximation of recently developed HCV Core Ag (Abbott Diagnostics, Germany) kit are determined successively as 94.3%, 97.9%, 99.1%, 87%, 95.3% and 88%. Although the new HCV Ag assay is clearly not sensitive enough to replace HCV NAT it may serve as a valuable tool in the HCV diagnostic algorithm as it is able to pick up a great majority of anti-HCV and HCV RNA positive samples, thus allowing a timely and less expensive serological diagnosis of an active HCV infection. This may be an advantage for labs that do not have access to PCR easily.