Impact of US Public Health Service increased risk deceased donor designation on organ utilization

Under US Public Health Service guidelines, organ donors with risk factors for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) are categorized as increased risk donors (IRD). Previous studies have suggested that IRD organs are utilized at lower rates than organs from standard risk donors (SRD), but these studies were conducted prior to universal donor nucleic acid test screening. We conducted risk‐adjusted analyses to determine the effect of IRD designation on organ utilization using 2010‐2017 data (21 626 heart, 101 160 kidney, 52 714 liver, and 16 219 lung recipients in the United States) from the Organ Procurement and Transplantation Network. There was no significant difference (P < .05) between risk‐adjusted utilization rates for IRD vs SRD organs for adult hearts and livers and pediatric kidneys, livers, and lungs. Significantly lower utilization was found among IRD adult kidneys, lungs, and pediatric hearts. Analysis of the proportion of transplanted organs recovered from IRD by facility suggests that a subset of facilities contribute to the underutilization of adult IRD kidneys. Along with revised criteria and nomenclature to identify donors with HIV, HBV, or HCV risk factors, educational efforts to standardize informed consent discussions might improve organ utilization.     

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.     

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.     

Transplantation of high‐risk donor organs: a survey of US solid organ transplant center practices as reported by transplant infectious diseases physicians

Abstract: Public Health Service (PHS) guidelines developed in 1994 provide guidance to minimize the risk of HIV transmission and to monitor recipients following the transplantation of “high‐risk” organs. There are no data on current practices or opinions of these policies by transplant infectious diseases (TID) physicians. An electronic survey was sent to all US solid organ transplatation centers with identified TID expertise as self‐reported to the American Society of Transplantation and Infectious Diseases Society of America. A total of 108 surveys were sent in December 2007 and 32 responses were received (30%). Thirty‐three percent of centers obtain only verbal, 52% verbal and written, and 14% do not obtain any special consent from recipients of organs from high‐risk donors (ROHRD). Post‐solid organ transplantation serologies for HIV, hepatitis B (HBV), and hepatitis C virus (HCV) are obtained at 40% of centers in ROHRD only, 20% in all recipients, and not performed in 40%; post‐solid organ transplantation nucleic acid testing (NAT) testing is carried out in 36–45% of centers in ROHRD, 11% in all recipients, and not performed in approximately 50% of centers. Only 22.7% of respondents believed current guidelines accurately represent what they consider to be high‐risk donors. There is significant variability in the acceptance and management of ROHRD in the US. Most TID experts do not feel that the current PHS guidelines accurately define high‐risk donors.     

Accepting hepatitis C virus–infected donor hearts for transplantation: Multistep consent,unrealized opportunity,and the Stanford experience

The current mismatch between supply and demand of organs has prompted transplant clinicians to consider innovative solutions to broaden the donor pool. Advancements of direct‐acting antiviral agent (DAA) therapy for hepatitis C virus (HCV) have allowed entertaining the use of viremic donor organs in nonviremic recipients. In this report, we describe the evolution of HCV treatment, ethics and informed consent, cost‐effectiveness of HCV medications in treating acute HCV post‐transplantation, and the Stanford experience with two HCV‐viremic donor heart transplantations. We describe excellent short‐term outcomes post–heart transplantation with HCV NAT‐positive organs. The availability of this therapy may expand the donor pool. While we await larger‐scale clinical data on the effectiveness and safety of DAA therapy in patients after heart transplantation, many transplant centers have already started accepting organs from HCV‐infected donors, balancing the unknown long‐term risks versus the benefits of shorter wait times and expansion of the donor pool. Protocols and multidisciplinary teams are needed to effectively communicate risk to potential recipients, to ensure timely DAA access, and to implement appropriate clinical follow‐up in order to achieve excellent clinical outcomes and to maximize the donor pool by utilizing HCV‐infected organs for heart transplantation.     

Transmission of Human Immunodeficiency Virus and Hepatitis C Virus From an Organ Donor to Four Transplant Recipients

In 2007, a previously uninfected kidney transplant recipient tested positive for human immunodeficiency virus type 1 (HIV) and hepatitis C virus (HCV) infection. Clinical information of the organ donor and the recipients was collected by medical record review. Sera from recipients and donor were tested for serologic and nucleic acid‐based markers of HIV and HCV infection, and isolates were compared for genetic relatedness. Routine donor serologic screening for HIV and HCV infection was negative; the donor's only known risk factor for HIV was having sex with another man. Four organs (two kidneys, liver and heart) were transplanted to four recipients. Nucleic acid testing (NAT) of donor sera and posttransplant sera from all recipients were positive for HIV and HCV. HIV nucleotide sequences were indistinguishable between the donor and four recipients, and HCV subgenomic sequences clustered closely together. Two patients subsequently died and the transplanted organs failed in the other two patients. This is the first recognized cotransmission of HIV and HCV from an organ donor to transplant recipients. Routine posttransplant HIV and HCV serological testing and NAT of recipients of organs from donors with suspected risk factors should be considered as routine practice.     

Liver transplantation for hepatitis C virus (HCV) non‐viremic recipients with HCV viremic donors

In the context of organ shortage, the opioid epidemic, and effective direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV‐infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor‐derived HCV in previously non‐viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor‐derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non‐viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA‐based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20–59). There have been no instances of graft loss or death, with median follow‐up of 380 days (IQR 263–434) posttransplant. Transplantation of HCV‐viremic livers into non‐viremic recipients results in acceptable short‐term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.     

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 12 months and all are NAT‐ to date. One recipient developed reactive HCV Ab at 6 months 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.     

Transplant Infectious Diseases: A Review of the Scientific Registry of Transplant Recipients Published Data

The Scientific Registry of Transplant Recipients (SRTR) serves to collect data on organ transplants performed in the United States. Although the infectious diseases data are limited and include mostly pretransplant serologies and other nonspecific infection‐related outcomes, this multicenter data collection allows for insightful national data and the ability to monitor trends over time. We reviewed the published concise reports for each organ type in SRTR reports containing data from 2005 to 2014, and summarized our findings with respect to cytomegalovirus (CMV), Epstein‐Barr virus, posttransplant lymphoproliferative disorder (PTLD), hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, general infection, and prophylaxis. Our review highlights a few developments. While rates of donor–recipient CMV serology combinations remain fairly constant over time, there are generally more seronegative donors and recipients among living donor transplants. There has been a reduction in PTLD for pediatric transplant recipients. There has also been a slight reduction in anti‐HBV core antibody–positive donor organs and stable reporting of HCV‐positive donor organs and HIV‐positive recipients.     

Transplanting kidneys from donors with prior hepatitis B infection: one response to the organ shortage

While the number of cadaveric organ donors remains relatively stable, the number of patients awaiting transplantation continues to increase, creating a shortage of donor organs. To address this imbalance, there is interest in transplanting organs formerly considered marginal or undesirable. Thus, more organs are currently transplanted from living donors, older donors, hemodynamically unstable donors, non-heart-beating donors and donors with markers of prior hepatitis B virus (HBV) infection. A large number (up to 93.8%) of liver transplant seronegative recipients from anti-HBc antibody positive donors have acquired HBsAg after liver transplantation in the absence of immunoprophylaxis. Based on experience in liver transplantation programs, transmission of HBV from donors without HBsAg but with antibody to HBV core antigen (anti-HBc), although conventionally defined as evidence of resolved infection, can have adverse consequences on both graft and recipient. On the contrary, HBV appears to be in-frequently transmitted from HBsAg negative/anti-HBcAb positive kidney donors: the incidence of de novo HBsAg seropositivity after renal transplantation ranges between 0 and 5.2%. A significantly higher incidence of anti-HBc antibody seroconversion (without developing HBsAg) after renal transplantation with anti-HBc antibody positive donors was seen. However, anti-HBc antibody positive renal allografts should be considered, especially for recipients who have been successfully immunized with HBV vaccine. Prospective long-term studies are in progress to assess the risk of de novo HBV infection (HBsAg seroconversion) in renal transplant recipients who have not been successfully immunized with vaccine against HBV.     

Dual hepatitis virus infections in liver transplant: case report and a review of the literature

Abstract: Background: Liver transplantation (LT) using grafts from anti‐HBVcore antibody‐positive (anti‐HBVcAB+) donors carry risk for development of hepatitis B virus (HBV) infection. The long‐term course of hepatitis C virus (HCV) patients receiving anti‐HBVcAB+ grafts is poorly understood. Patients and methods: A patient with chronic hepatitis C received an anti‐HBVc+ graft and developed de novo hepatitis B after four months. We describe the 14 HCV patients who received antiHBVc+ grafts and the condition of disease. Results: Hepatitis B was treated successfully with lamivudine. One year later, breakthrough infection developed with a lamivudine‐resistant mutant. Addition of adefovir led to HBV surface antigen to surface antibody seroconversion after two yr, which was maintained long term. Antiviral therapy was discontinued. Liver biopsy revealed minimal histologic changes up to eight yr post‐LT. Survival of 14 recipients of antiHBVc+ allografts and 180 recipients of antiHBVc‐negative grafts was equal (minimum follow up of five yr). Liver biopsies at four yr showed grade 0/1 and stage 0/1 in >70%; only two patients showed bridging fibrosis. A literature review of dual hepatitis virus infection revealed an overall milder course of hepatitis post‐LT. Conclusion: The outcome of HCV patients receiving anti‐HBc+ grafts is good and may be associated with a milder course of recurrent HCV.     

Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: a prospective study

Hepatitis C virus (HCV) positive donors are identified in Spain by antibody detection (HCV‐Ab) techniques while a HCV nuclear acid‐testing (HCV‐NAT) is not mandatory. Since it has been shown that HCV‐Ab positive HCV‐NAT negative donors do not universally transmit the infection, we designed a protocol based on the identification of viremia in HCV‐Ab positive donors to start treatment if needed. HCV‐Ab‐positive donors were identified and we performed HCV‐NAT immediately. Donors coinfected with HIV were excluded. Recipients with a low chance to receive a transplant, with no history of liver disease and who were negative for HCV‐Ab were selected after informed consent was signed. Kidney recipients from HCV‐NAT‐positive donors received glecaprevir and pibrentasvir from 6 h before the transplant until 8 weeks after. Recipients from HCV‐NAT‐negative donors were not treated. Regular monitoring by HCV‐NAT was performed to initiate antiviral treatment. We included 11 recipients from six deceased donors Four recipients received grafts from HCV‐NAT‐positive donors and seven patients received grafts from HCV‐NAT‐negative donors. None of our recipients exhibited HCV‐NAT positivity during the minimum follow‐up period of 6 months. Recipients from HCV‐NAT‐positive donors exhibited sustained virologic response at 12 weeks. One recipient from an HCV‐NAT‐negative donor lost his graft via a process thought to be unrelated to HCV. The remaining 10 patients had a stable functioning graft at the end of the follow‐up period. Our preliminary data suggest that renal transplantation from HCV‐Ab‐ positive donors to HCV‐Ab negative recipients is safe when only the recipients of organs from HCV‐NAT‐positive donors are treated.     

肾移植供者及受者肝炎等病毒和螺旋体感染的调查

目的 调查肾移植供、受者肝炎病毒及其他病毒感染和螺旋体感染的情况,研究其感染与移植术后人／肾存活率的关系。方法 对供者及移植受者群进行乙型肝炎（HBV）、丙型肝炎（HCV）、庚型肝炎病毒（HGV）及巨细胞病毒（CMV）、EB病毒、单纯庖疹病毒（HSV）、艾滋病病毒（HIV）、梅毒螺旋体（RPR）的调查。结果 361名供者中,感染HBV者8.6%,感染HCV者2.5％,感染HGV者0.6％;231名供者中,CMV－IgM阳性者16.9％,EB－IgM阳性者11.7％,HSV－IgV阳性者16.0％,HIV病毒携带者1名,RPR－IgM阳性者2名。300例移植受者中,HBV感染率为68.7％,HCV感染率为34.7％,HBV合并HCV感染率为25.0％,HGV、HBV合并HCV感染率为12.5％,CMV－IgM阳性者49.0％,EB－IgM阳性者32.7％,HSV－IgM阳性者42.0％,无HIV携带者及RPR－IgM阳性者49.0％,EB－IgM阳性者32.7％,HSV-IgM阳性者42.0％,无HIV携带者及RPR－IgM阳性者。结论 供者群及受者本身的术前病毒感染状态对移植者术后是否发生病毒感染至关重要。     

Current state of kidney transplantation in patients with HIV,hepatitis C,and hepatitis B infection

Human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common chronic viral infections in the end-stage kidney disease (ESKD) patient population that were once considered relative contraindications to kidney transplantation. In this review, we will summarize the current state of kidney transplantation in patients with HIV, HCV, and HBV, which is rapidly evolving. HIV+ patients enjoy excellent outcomes in the modern transplant era and may have new transplant opportunities with the use of HIV+ donors. Direct-acting antivirals for HCV have substantially changed the landscape of care for patients with HCV infection. HBV+ patients now have excellent patient and allograft survival with HBV therapy. Currently, kidney transplantation is a safe and appropriate treatment for the majority of ESKD patients with HIV, HCV, and HBV.     

Liver transplantation for HBsAg‐positive recipients using grafts from HBsAg‐positive deceased donors

This study reports our experience using deceased donor liver grafts from HBsAg‐positive donors. We performed eight cases of liver transplantation (LT) using grafts from deceased HBsAg‐positive donors between November 2005 and October 2010. The median age of donors was 48 years (range: 26–64). HBV DNA in the serum of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative. Preoperative laboratory and liver biopsy samples revealed the absence of definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive preoperatively except one patient with HBsAg(?) status post previous LT for HBV related liver cirrhosis. The median age was 60 years (range: 46–76) at LT. Post‐LT antiviral management consisted of hepatitis B immunoglobulin and antiviral nucleos(t)ide analogues. The median follow‐up period was 25.5 months (range: 14–82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA disappearance postoperatively. Three recipients died of HBV‐unrelated causes. The remaining five recipients were stable with normal liver function and no marked pathologic changes on follow‐up biopsies. This experience shows that LT using grafts from deceased HBsAg‐positive donors is feasible, and may represent a valuable expansion of the pool of organ donors with appropriate antiviral management and monitoring.     

Inferior graft survival of hepatitis B core positive grafts is not influenced by post‐transplant hepatitis B infection in liver recipients—A 35‐year single‐center experience

Nonoptimal liver grafts, and among them organs from anti‐HBc+ donors, are increasingly used for liver transplantation. In this retrospective study including 1065 adult liver transplantations performed between 1977 and 2012, we analyzed long‐term patient and graft survival and occurrence of HBV infection. A total of 52 (5.1%) patients received an anti‐HBc+ graft. The 10‐year graft and patient survival of these recipients were 50.9% and 59.0% compared to 72.0% and 76.5% (P = 0.001; P = 0.004) of patients receiving anti‐HBc‐ grafts, respectively. Cox regression model showed that high urgency allocation (P = 0.003), recipient age (P = 0.027), anti‐HCV+ recipients (P = 0.005), and anti‐HBc+ organs (P = 0.048) are associated with decreased graft survival. Thirteen of 52 (25.0%) patients receiving anti‐HBc+ grafts developed post‐transplant HBV infection within a mean of 2.8 years. In this study, antiviral prophylaxis did not have significant impact on HBV infection, but long‐term survival (P = 0.008). Development of post‐transplant HBV infection did not affect adjusted 10‐year graft survival (100% vs. 100%; P = 1). Anti‐HBc+ liver grafts can be transplanted with reasonable but inferior long‐term patient and graft survival. The inferior graft survival is not, however, related with post‐transplant HBV infection as long as early diagnosis and treatment take place.     

Process of selecting and educating HCV‐uninfected kidney waiting‐list candidates for HCV‐infected kidney transplantation

Long waiting times for kidney transplant (KT) and the high risk of mortality on dialysis have prompted investigation into strategies to utilize hepatitis C virus (HCV)‐infected organs to decrease discard rates of potentially viable kidneys. Due the opioid epidemic, the number of HCV‐infected donors has increased significantly. With the development of direct‐acting antiviral therapies for HCV infection, now more than 95% of patients who received treatment are cured. Experimental trials have used direct‐acting antiviral therapy to treat HCV infection in HCV‐uninfected transplant recipients of kidneys from HCV‐viremic donors. To date, HCV has been eradicated in all cases. Though these strategies will potentially increase the donor pool of available kidneys, shorten waitlist times, and ultimately decrease mortality in patients waiting for KT, identifying the ideal candidates and educating them about a protocol to utilize direct‐acting antiviral therapy to cure HCV after it is transmitted is essential. We present our approach to patient selection and education for a clinical trial in transplantation of HCV viremic kidneys into uninfected recipients.     

Transplantation of kidneys from hepatitis C‐positive donors into hepatitis C virus‐infected recipients followed by early initiation of direct acting antiviral therapy: a single‐center retrospective study

The availability of direct acting antiviral agents (DAA) has transformed the treatment of hepatitis C virus (HCV) infection. The current study is a case series that reports the outcomes from a cohort of twenty‐five HCV‐infected ESRD patients who received a kidney from an anti‐HCV‐positive deceased organ donor followed by treatment with DAAs in the early post‐transplant period. Time to transplantation and the efficacy of DAA therapy as measured by sustained viral response at 12 weeks were assessed. The median waiting time from original date of activation on the United Network Organ Sharing (UNOS) waiting list until transplantation was 427 days; however, the median time from entering the patient into UNet^sm for a HCV‐positive offer until transplantation was only 58 days. The 25 patients were started on antiviral treatment early post‐transplant (median 125 days) and 24 of 25 (96%) achieved a sustained virologic response at 12 weeks. Tacrolimus dose adjustments were required during antiviral treatment in 13 patients to maintain therapeutic levels. Accepting a kidney from an anti‐HCV‐positive deceased donor shortened the waiting time for HCV‐infected kidney transplant candidates. We recommend that kidneys from anti‐HCV‐positive donors should be considered for transplant into HCV‐infected recipients followed by early post‐transplant treatment with DAA agents.     

Allowing HIV‐Positive Organ Donation: Ethical,Legal and Operational Considerations

Case reports of kidney transplantation using HIV‐positive (HIV+) donors in South Africa and advances in the clinical care of HIV+ transplant recipients have drawn attention to the legal prohibition of transplanting organs from HIV+ donors in the United States. For HIV+ transplant candidates, who face high barriers to transplant access, this prohibition violates beneficence by placing an unjustified limitation on the organ supply. However, transplanting HIV+ organs raises nonmaleficence concerns given limited data on recipient outcomes. Informed consent and careful monitoring of outcome data should mitigate these concerns, even in the rare circumstance when an HIV+ organ is intentionally transplanted into an HIV‐negative recipient. For potential donors, the federal ban on transplanting HIV+ organs raises justice concerns. While in practice there are a number of medical criteria that preclude organ donation, only HIV+ status is singled out as a mandated exclusion to donation under the National Organ Transplant Act (NOTA). Operational objections could be addressed by adapting existing approaches used for organ donors with hepatitis. Center‐specific outcomes should be adjusted for HIV donor and recipient status. In summary, transplant professionals should advocate for eliminating the ban on HIV+ organ donation and funding studies to determine outcomes after transplantation of these organs.     

National landscape of HIV+ to HIV+ kidney and liver transplantation in the United States

The HIV Organ Policy Equity (HOPE) Act, enacted on November 21, 2013, enables research on the transplantation of organs from donors infected with human immunodeficiency virus (HIV) (HIV+) into HIV+ individuals who, prior to transplantation, are infected with HIV. In 2015, the Organ Procurement and Transplantation Network revised organ allocation policies on November 21, and on November 23, the Secretary of Health and Human Services published research criteria and revised the Final Rule accordingly. The HOPE Act appears to be underutilized to date. As of December 31, 2018, there were 56 donors recovered (50 donors transplanted) resulting in 102 organs transplanted (31 liver, 71 kidney). As of December 31, 2018, 212 registrations were indicated on the waiting list as willing to accept an HIV+ kidney or liver, most of which were waiting in active status. Due to the limited number of transplants performed to date, definitive safety conclusions cannot be reached at this time, though current data suggest that 1‐year patient and graft survival does not deviate in a major way from that observed in HIV+ recipients of non‐HIV+ organs or non‐HIV+ recipients. As safety data are reviewed and disseminated, it is anticipated that HOPE participation will increase should safety signals remain low.