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.     

The Outcomes of Kidney Transplantation in Hepatitis B Surface Antigen (HBsAg)–Negative Recipients Receiving Graft From HBsAg‐Positive Donors: A Retrospective,Propensity Score‐Matched Study

The outcomes of kidney transplantation (KT) from hepatitis B surface antigen–positive [HBsAg(+)] donors to HBsAg(?) recipients remain inconclusive, possibly due to substantial differences in methodological and statistical models, number of patients, follow‐up duration, hepatitis B virus (HBV) prophylactic regimens and hepatitis B surface antibody (anti‐HBs) levels. The present retrospective, longitudinal study ( clinicaltrial.gov NCT02044588) using propensity score matching technique was conducted to compare outcomes of KT between HBsAg(?) recipients with anti‐HBs titer above 100 mIU/mL undergoing KT from HBsAg(+) donors (n = 43) and HBsAg(?) donors (n = 86). During the median follow‐up duration of 58.2 months (range 16.7–158.3 months), there were no significant differences in graft and patient survivals. No HBV‐infective markers, including HBsAg, hepatitis B core antibody, hepatitis B extracellular antigen and HBV DNA quantitative test were detected in HBsAg(+) donor group. Renal pathology outcomes revealed comparable incidences of kidney allograft rejection while there were no incidences of HBV‐associated glomerulonephritis and viral antigen staining. Recipients undergoing KT from HBsAg(+) donors with no HBV prophylaxis (n = 20) provided comparable outcomes with those treated with lamivudine alone (n = 21) or lamivudine in combination with HBV immunoglobulin (n = 2). In conclusion, KT without HBV prophylaxis from HBsAg(+) donors without hepatitis B viremia to HBsAg(?) recipients with anti‐HBs titer above 100 mIU/mL provides excellent graft and patient survivals without evidence of HBV transmission.

     

Successful Lung Transplantation From Hepatitis C Positive Donor to Seronegative Recipient

Lung transplantation using RNA+ hepatitis C (HCV+) donors to seronegative recipients is not currently performed due to the very high risk of transmission. Previous reports have shown poor survival when this practice was applied. The emergence of new direct‐acting antiviral drugs (DAA) suggests a high chance of sustained virologic response in immunocompetent patients. We report here successful transplantation of lungs from HCV+ donor to HCV? recipient. The recipient was an HCV? patient with chronic lung allograft dysfunction. Viral transmission occurred early posttransplant but excellent clinical outcomes were observed including elimination of HCV after 12 weeks of treatment using DAAs.     

Donor‐Derived Strongyloides stercoralis Infection in Solid Organ Transplant Recipients in the United States, 2009–2013

Infection with Strongyloides stercoralis is typically asymptomatic in immunocompetent hosts, despite chronic infection. In contrast, immunocompromised hosts such as solid organ transplant recipients are at risk for hyperinfection syndrome and/or disseminated disease, frequently resulting in fatal outcomes. Infection in these recipients may result from reactivation of latent infection or infection through transmission from an infected donor. We describe the Centers for Disease Control and Prevention's experience with seven clusters of donor‐derived infection from 2009 to 2013. Six of the seven (86%) donors were born in Latin America; donor screening was not performed prior to organ transplantation in any of these investigations. Eleven of the 20 (55%) organ recipients were symptomatic, two of whom died from complications of strongyloidiasis. We also describe the New York Organ Donor Network (NYODN) experience with targeted donor screening from 2010 to 2013. Of the 233 consented potential donors tested, 10 tested positive for Strongyloides antibody; and 18 organs were transplanted. The majority (86%) of the donors were born in Central or South America. Fourteen recipients received prophylaxis after transplantation; no recipients developed strongyloidiasis. The NYODN experience provides evidence that when targeted donor screening is performed prior to transplantation, donor‐derived infection can be averted in recipients.     

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.     

Coccidioidomycosis Transmission Through Organ Transplantation: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee

Donor‐derived coccidioidomycosis has caused unexpected morbidity and mortality in transplant recipients. All proven or probable reports of donor‐derived coccidioidomycosis to the Disease Transmission Advisory Committee between 2005 and August 2012 were reviewed. Six reports of proven or probable coccidioidomycosis were discovered. In four of six, the infection was first detected at autopsy in the recipient. In two cases it was first identified in the donor. Twenty‐one recipients received organs from these six donors. Transmission occurred in 43% at a median of 30 days posttransplant with a mortality rate of 28.5%. Eleven recipients received preemptive antifungals, seven did not receive treatment, and treatment information was not reported for three recipients. Five of seven who did not receive prophylaxis/treatment died and all 11 who received early therapy survived. Six deaths occurred 14 to 55 days after transplant, with a median of 21 days. For exposed recipients, donor‐derived coccidioidomycosis is a significant cause of morbidity and mortality. Evidence of infection in one recipient should prompt immediate evaluation for treatment of all other recipients from the same donor as preemptive treatment was effective. Further studies are needed to decide whether all donors from endemic areas should have routine serologic screening.     

Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem‐Resistant Gram‐Negative Bacteria

Donor‐derived infections due to multidrug‐resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2‐year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem‐resistant gram‐negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor‐derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high‐risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high‐risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug‐resistant bacteria requires intra‐ and inter‐institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.     

Transplantation of hepatitis C virus (HCV) antibody positive,nucleic acid test negative donor kidneys to HCV negative patients frequently results in seroconversion but not HCV viremia

Anecdotal reports have suggested that transplantation of hepatitis C virus (HCV) antibody positive (Ab+)/nucleic acid test negative (NAT?) donor kidneys into HCV negative recipients is not associated with HCV transmission. We reviewed our center's outcomes of 32 HCV negative patients who received kidney allografts from 25 donors who were HCV Ab+/NAT?. The mean recipient age was 56.9 ± 12.1 years and the mean donor age was 41.5 ± 14 years, with a median Kidney Donor Profile Index (KDPI) of 68%. Twelve donors (48%) met Public Health Service (PHS) increased risk status. All patients received antithymocyte globulin induction followed by tacrolimus, mycophenolate mofetil, and steroid maintenance immunosuppression. With a mean follow‐up posttransplant of 10 ± 2.7 months, 1‐ and 3‐ month serum creatinine levels were 1.7 ± 0.8 and 1.3 ± 0.4, respectively, and patient and graft survival rates were 100% and 97%, respectively. Fourteen patients (44%) seroconverted and became HCV Ab+ posttransplant. However, all 32 patients were HCV RNA negative at 1‐ and 3‐ months posttransplant, and 27 and 8 patients tested at 6‐ and 12‐months posttransplant, respectively, remain HCV RNA negative. In conclusion, transplantation of HCV Ab+/NAT? kidneys to HCV negative recipients frequently causes HCV Ab seroconversion but not HCV viremia.     

Successful Recovery of Acute Renal Transplant Failure in Recurrent Hepatitis C Virus–Associated Membranoproliferative Glomerulonephritis

Recurrence of hepatitis C virus (HCV)–associated membranoproliferative glomerulonephritis (MPGN) in the kidney transplant may lead to continuous graft deterioration and the need for further renal replacement therapy. The novel direct‐acting antiviral agents (DAAs) allow a highly effective and interferon‐free treatment option for chronic HCV‐infected patients. Data on the therapeutic safety and efficacy in HCV‐infected renal transplant patients are sparse, especially for patients with severe renal impairment. We report the case of a 63‐year‐old female HCV‐positive renal transplant patient with biopsy‐proven recurrence of MPGN in the renal graft 3 years after transplant. Because of rapid loss of transplant function and consecutive need for hemodialysis, we initiated a combined anti‐HCV–directed therapy regimen consisting of daclatasvir and simeprevir over 12 weeks. Viral clearance of HCV was obtained as early as 2 weeks after start of treatment. No adverse therapy‐associated side effects were observed, and immunosuppressive dosing remained unchanged. Importantly, graft function fully recovered and hemodialysis was stopped 2 mo after the end of daclatasvir/simeprevir treatment. We report the first case of successful recovery of dialysis‐dependent renal transplant failure after treatment of recurrent HCV‐associated MPGN in a kidney transplant recipient by curing the underlying HCV infection with a combination of novel DAAs.     

Arenaviruses and West Nile Virus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the epidemiology, diagnosis, prevention, and management of infection due to Arenaviruses and West Nile Virus (WNV) in the pre‐ and post‐transplant period. Arenaviruses and WNV have been identified as causes of both donor‐derived and post‐transplant infection. Most data related to these infections have been published in case reports and case series. Transplant recipients may become infected with Arenaviruses if they, or their donors, are exposed to wild rodents or infected pet rodents. Lymphocytic choriomeningitis virus is the most commonly recognized Arenavirus among transplant recipients and should be considered when transplant recipients present with fever, hepatitis, meningitis/encephalitis, and/or multisystem organ failure. WNV is a mosquito‐borne virus, and as such, its incidence varies yearly depending on environmental conditions. WNV in transplant recipients typically presents with fever, myalgias, and rash; approximately one in 40 develop neuroinvasive disease. Due to its morbidity, the Organ Procurement and Transplantation Network recently mandated that transplant centers screen living donors for WNV infection in endemic areas. Little is known about the optimal treatment of Arenaviruses or WNV; reduction in immunosuppression and supportive care are the mainstays of management at present.