The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

Current practices for treatment of respiratory syncytial virus and other non-influenza respiratory viruses in high-risk patient populations: a survey of institutions in the Midwestern Respiratory Virus Collaborative.

BACKGROUND: The optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non-influenza respiratory viruses in Midwestern transplant centers. METHODS: A survey assessing strategies for RSV and other non-influenza respiratory viral infections was sent to 13 centers. RESULTS: Multiplex polymerase chain reaction assay was used for diagnosis in 11/12 centers. Eight of 12 centers used inhaled ribavirin (RBV) in some patient populations. Barriers included cost, safety, lack of evidence, and inconvenience. Six of 12 used intravenous immunoglobulin (IVIG), mostly in combination with RBV. Inhaled RBV was used more than oral, and in the post-stem cell transplant population, patients with lower respiratory tract infection (LRTI), graft-versus-host disease, and more recent transplantation were treated at higher rates. Ten centers had experience with lung transplant patients; all used either oral or inhaled RBV for LRTI, 6/10 treated upper respiratory tract infection (URTI). No center treated non-lung solid organ transplant (SOT) recipients with URTI; 7/11 would use oral or inhaled RBV in the same group with LRTI. Patients with hematologic malignancy without hematopoietic stem cell transplantation were treated with RBV at a similar frequency to non-lung SOT recipients. Three of 12 centers, in severe cases, treated parainfluenza and metapneumovirus, and 1/12 treated coronavirus. CONCLUSIONS: Treatment of RSV in immunocompromised patients varied greatly. While most centers treat LRTI, treatment of URTI was variable. No consensus was found regarding the use of oral versus inhaled RBV, or the use of IVIG. The presence of such heterogeneity demonstrates the need for further studies defining optimal treatment of RSV in immunocompromised hosts.

Transmission of Hepatitis C Virus From Organ Donors Despite Nucleic Acid Test Screening.

Nucleic acid testing (NAT) for hepatitis C virus (HCV) is recommended for screening of organ donors, yet not all donor infections may be detected. We describe three US clusters of HCV transmission from donors at increased risk for HCV infection. Donor's and recipients' medical records were reviewed. Newly infected recipients were interviewed. Donor-derived HCV infection was considered when infection was newly detected after transplantation in recipients of organs from increased risk donors. Stored donor sera and tissue samples were tested for HCV RNA with high-sensitivity quantitative PCR. Posttransplant and pretransplant recipient sera were tested for HCV RNA. Quasispecies analysis of hypervariable region-1 was used to establish genetic relatedness of recipient HCV variants. Each donor had evidence of injection drug use preceding death. Of 12 recipients, 8 were HCV-infected-6 were newly diagnosed posttransplant. HCV RNA was retrospectively detected in stored samples from donor immunologic tissue collected at organ procurement. Phylogenetic analysis showed two clusters of closely related HCV variants from recipients. These investigations identified the first known HCV transmissions from increased risk organ donors with negative NAT screening, indicating very recent donor infection. Recipient informed consent and posttransplant screening for blood-borne pathogens are essential when considering increased risk donors.

Education and informed consent about increased risk donor kidneys: a national survey of non-physician transplant providers.

INTRODUCTION: Transplant providers must understand the definition of increased risk donor (IRD) organs to effectively educate transplant candidates and obtain informed consent. This study surveyed non-physician providers from 20 transplant centers about their educational and informed consent practices of IRD kidneys. METHODS: An anonymous, web-based survey about the content and timing of education and informed consent for potential recipients of IRD kidneys, providers' knowledge of IRD kidneys, and provider and center characteristics was completed by most (67%; 90 of 135) of those invited to participate; 87 responses were included in analysis. RESULTS: Most (80%) reported understanding the concept of IRD kidneys. However, few reported sufficient knowledge of the Organ Procurement and Transplantation Network definition of IRDs, risk factors, screening tests, window periods, and infection transmission rates. Most (56%) felt uncomfortable with obtaining specific informed consent for IRD kidneys. Most respondents received informal education about IRD kidneys (78%), and recognized the need for (98%) and were interested in receiving (99%) further education on this topic. CONCLUSION: Non-physician transplant providers need and are interested in better education about IRD kidneys to effectively educate patients and obtain patients' informed consent.

Screening recipients of increased-risk donor organs: a survey of transplant infectious diseases physician practices.

BACKGROUND: In 1994, the Public Health Service published guidelines to minimize the risk of human immunodeficiency virus (HIV) transmission and to monitor recipients following the transplantation of organs from increased-risk donors. A 2007 survey revealed the post-transplant surveillance of recipients of organs from increased-risk donors (ROIRD) is variable. METHODS: An electronic survey was sent to transplant infectious diseases physicians at US solid organ transplant centers. RESULTS: A total of 126 surveys were sent to infectious diseases physicians, and we received 51 (40%) responses. We found that 22% of respondents obtain only verbal, 69% verbal and written, and 8% do not obtain any special consent from ROIRD, despite an Organ Procurement and Transplantation Network policy requiring such consent. Post-solid organ transplantation serologies for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) are performed by 6-8% of respondents in all recipients, by 69% of respondents in ROIRD only, and 25% of respondents do not perform them at all. Post-transplant nucleic acid testing is carried out by 55-64% of respondents in ROIRD, by 0-2% in all recipients, and not performed by 35-43% of respondents. CONCLUSION: Screening RIORD for HIV, HBV, and HCV has increased since 2007, but remains less than optimal and is incomplete when screening for disease transmission at many centers.

Deceased organ donor screening for HIV, hepatitis B, and hepatitis C viruses: a survey of organ procurement organization practices.

Although Organ Procurement and Transplantation Network (OPTN) policy requires that all potential deceased organ donors are screened for human immunodeficiency (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses by serology, no current policy requires the use of nucleic acid testing (NAT) for organ donor screening. An electronic survey was sent to 58 organ procurement organizations (OPO) in the United States to assess current screening practices of potential deceased organ donors. Fifty-seven responses were collected for data analysis; not all respondents answered all questions. All OPOs performed required HIV, HBV and HCV serology screening and 48 (84%) performed confirmatory testing for seropositive donors. Ninety-eight percent, 75% and 97% of OPOs performed prospective HIV, HBV and HCV NAT, respectively. Fifty-two percent and 47% used a transcription-mediated amplification assay for HIV and HCV NAT, respectively. Of the 56 respondents that performed HIV NAT and 55 respondents that performed HCV NAT, 39 tested all donors. Seventeen (32%) OPOs performed confirmatory testing for all HIV-positive NAT results, and 15 (27%) OPOs performed confirmatory testing for all HCV-positive NAT results. Since 2008, the number of OPOs performing NAT has increased and more OPOs are testing all donors.

BK virus replication and nephropathy after alemtuzumab-induced kidney transplantation.

BK virus nephropathy (BKVN) is a recognized cause of graft failure in kidney transplant recipients. There are limited data on the epidemiology of BK virus (BKV) infection after alemtuzumab induction. By clinical protocol, the kidney transplant recipients at our center were screened with BKV plasma PCR monthly for the first 4 months posttransplant then every 2-3 months for 2 years. A single center retrospective cohort study of all kidney transplant recipients from January 2008 to August 2010 was conducted to determine incidence and outcomes of BKV infection. Descriptive statistics and Kaplan-Meier analysis was performed. Of 666 recipients, 250 (37.5%) developed viruria, 80 (12%) developed viremia and 31 (4.7%) developed BKVN at a median of 17, 21 and 30 weeks, respectively. Induction with alemtuzumab did not significantly affect incidence of BKVN. Increased recipient age, African American race, acute graft rejection and CMV infection were significantly associated with the development of BKVN in multivariate analysis. The incidence of BK viruria, viremia and nephropathy was not significantly different among kidney transplant recipients who received alemtuzumab induction compared to patients receiving less potent induction.

Use of the QuantiFERON-TB Gold interferon-gamma release assay for screening transplant candidates: a single-center retrospective study.

BACKGROUND: Tuberculosis (TB) reactivation is a rare but significant complication of organ transplantation, and screening of all transplant candidates for latent infection is recommended with either an interferon-γ release assay (IGRA) or tuberculin skin test (TST). METHODS: After institutional review board approval, we retrospectively collected data to describe the yield of transplant candidate screening using the QuantiFERON-TB Gold (QFT) and QuantiFERON-TB Gold In-Tube (QFT-IT) assays since the institution of TB screening in 2008 and the epidemiology of all cases of post-transplant TB in our institution since 2004. RESULTS: A total of 2392 patients were screened with either the QFT or QFT-IT assay through October 2009; 245 (10.2%) tested positive and 206 (8.6%) were indeterminate. Of those with positive results, 107 (43.7%) were foreign born and most of the remainder had prior TB exposures. Of the tests performed at a reference lab, 29% were indeterminate, whereas 14% were indeterminate using our in-house lab. The majority of indeterminate results were seen in liver transplant candidates (40.6% vs. 11.8% in non-liver candidates). Three of 694 (0.43%) screened patients who underwent transplantation developed TB post transplant. CONCLUSIONS: Post-transplant TB occurs at a low rate with universal IGRA-based candidate screening, which is comparable to studies using TST screening.

The challenge of informed consent for increased risk living donation and transplantation.

The Organ Procurement and Transplantation Network (OPTN) mandates that organ recipients provide "specific informed consent" before accepting organs that the OPTN defines as "increased risk". However, the OPTN does not provide specific guidelines for what information should be disclosed to potential recipients. Such vagueness opens the door to inadequate informed consent. This paper examines the ethical dimensions of informed consent when the prospective living donor has self-reported behaviors associated with increased risk for infection transmission. Donor privacy is a primary ethical concern that conflicts with recipients' informed consent for use of increased risk organs. We propose that both the increased risk status and the specific behavior be disclosed to the recipient. Because the actual risk posed is linked to the type of risk behavior, disclosure is therefore needed to make an informed decision. The donor's risk behavior is material to recipients' decision making because it may impact the donor-recipient relationship. This relationship is the foundation of the donation and acceptance transaction, and thus comprises a critical feature of the recipient's informed consent. Optimizing a recipient's informed consent is essential to protecting patient safety and autonomy.