Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

Pseudomonas aeruginosa ventricular assist device infections: findings from ineffective phage therapies in five cases.

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Using HCV-viremic organs for lung transplantation does not confer higher rejection rates compared to HCV-negative organs.

BACKGROUND: National data demonstrate that hepatitis C virus (HCV)-infected organ donors are increasingly being used in the US, including for lung transplantation. We aimed to assess whether there were any differences in the acute or chronic rejection rates at 1 year following lung transplantation from HCV-viremic versus uninfected donors. METHODS: We retrospectively reviewed all lung transplant recipients at our institution from April 1, 2017 to October 1, 2020 and then assessed various outcomes between those who received a transplant from HCV-viremic donors versus HCV-negative donors. Primary outcome was to determine if there was a higher incidence of acute and/or chronic allograft rejection when using HCV NAT+ lung donation. We carried out univariate and multivariate analyses. RESULTS: We transplanted 135 patients during the study period, including 18 from HCV-viremic donors. Standard induction therapy with basiliximab and maintenance triple drug immunosuppression was utilized per UC San Diego protocol. All 17 patients receiving HCV-viremic organs developed acute HCV infection and were treated in the postoperative period with 12 weeks of direct acting antivirals (DAA). HCV genotypes included 1, 2, and 3. DAA used included glecaprevir/pibrentasvir (12), sofosbuvir/velpatasvir (1), and ledipasvir/sofosbuvir (2) with drug choice determined by patient's medical insurance coverage. Sustained virological response at 12 weeks after end of DAA therapy (SVR12), indicative of a cure, was achieved in all (100%) recipients. No recipient had a serious adverse event related to HCV infection. The lung transplant recipient (LTR) HCV-viremic donors had lower rates of clinically significant rejection (5.9% vs. 11% LTR HCV-nonviremic donors), and no chronic lung allograft dysfunction at 1 year (vs. 5.9% LTR HCV-nonviremic donors). One-year survival was 100% in the LTR HCV-viremic donors compared to 95.8% in the LTR HCV-nonviremic donors. CONCLUSIONS: We demonstrate the feasibility and success of using HCV NAT + donors with excellent results and without a higher incidence of rejection. Longer term follow-up and a larger sample size are needed to allow this to be a more widely accepted practice for lung transplant programs and payors.

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

BACKGROUND: 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-). METHODS: 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) ≥ 0.5 mm was considered significant for subclinical disease. RESULTS: 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. CONCLUSION: 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.

Designing and analyzing studies of coronavirus disease 2019 and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 among immunocompromised individuals.

Observational studies of coronavirus disease 2019 (COVID-19) among transplant candidates and recipients remain important as immunocompromised patients formed a very small proportion of patients included in COVID-19 trials and large database analyses. We discuss methods that have been used in such analyses to evaluate the impact of vaccination on the risk of symptomatic COVID-19 in such patients and on the probability of developing post-acute sequelae of severe acute respiratory syndrome coronavirus 2 after the onset of infection. We also propose future directions for research and discuss the methods that will be useful to conduct such investigations. The study design and analytical issues that we consider have the potential to be helpful not only for COVID-19 research but also for other infections as well.

Difference in immunosuppressant dose requirement when transitioning to isavuconazole from other azoles in thoracic transplant recipients.

The triazole antifungal isavuconazole (ISAVU) is used for prevention and treatment of fungal infections in solid organ transplant (SOT). SOT recipients commonly need to transition from one azole to another due to breakthrough infection, toxicity, or other reasons. The purpose of our study was to evaluate the effect of ISAVU on immunosuppressant concentrations in thoracic transplant recipients when ISAVU was started de novo or transitioned from another azole. We conducted a single-center retrospective cohort study including 68 patients (51 lung, 14 heart, and 3 heart/lung transplant). Concentration to dosage ratios (C/D) of immunosuppressants were assessed at baseline, day 3, and weekly for 9 weeks. When starting ISAVU de novo, we observed a temporary doubling of tacrolimus exposure. Cyclosporine and sirolimus required dose decreases. Tacrolimus C/D increased by 110% at day 3 in patients started on ISAVU de novo then returned to baseline C/D ± 17% weeks 2-9 (n = 8). One cyclosporine patient started on ISAVU de novo had variable C/D, and C/D increased by 219% ± 72% in 2 sirolimus patients. When transitioning from other azoles, tacrolimus and cyclosporine required about twice the initial dose. After week 1, tacrolimus C/D decreased by 53% ± 6% in patients transitioned from posaconazole (n = 33), voriconazole (n = 14), or fluconazole (n = 2). Cyclosporine C/D decreased by 45% ± 16% in patients transitioning from other azoles (posaconazole [n = 2], voriconazole [n = 2], fluconazole [n = 1]). Sirolimus C/D decreased by 73% ± 13% in patients transitioned from posaconazole (n = 7). Aside from the initial loading phase, ISAVU had a lesser degree of interaction with immunosuppressants than other azoles in loading phase, ISAVU had a lesser degree of interaction with immunosuppressants than other azoles in adjustments for the 4-week period after initiating antifungal therapy with ISAVU or switching from another agent.

Development of Host Immune Response to Bacteriophage in a Lung Transplant Recipient on Adjunctive Phage Therapy for a Multidrug-Resistant Pneumonia.

Bacteriophage therapy is the use of viruses to kill bacteria for the treatment of antibiotic-resistant infections. Little is known about the human immune response following phage therapy. We report the development of phage-specific CD4 T cells alongside rising phage-specific immunoglobulin G and neutralizing antibodies in response to adjunctive bacteriophage therapy used to treat a multidrug-resistant Pseudomonas aeruginosa pneumonia in a lung transplant recipient. Clinically, treatment was considered a success despite the development phage-specific immune responses.

HIV-Positive Liver Transplant Does not Alter the Latent Viral Reservoir in Recipients With Antiretroviral Therapy-Suppressed HIV.

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10). All measures remained stable from baseline by 1 year posttransplant. These data demonstrate that the LVR is stable after liver transplantation in people with HIV. Clinical Trials Registration. NCT02602262 and NCT03734393.

Phage Therapy in Lung Transplantation: Current Status and Future Possibilities.

Patients with chronic lung disease and lung transplantation have high rates of colonization and infection from multidrug-resistant (MDR) organisms. This article summarizes the current state of knowledge regarding phage therapy in the setting of lung transplantation. Phage therapy has been used in several lung transplant candidates and recipients on a compassionate use basis targeting mostly MDR gram-negative infections and atypical mycobacterial infections with demonstrated clinical safety. Phage biodistribution given intravenously or via nebulization has not been extensively studied, though preliminary data are presented. Phage interacts with both the innate and adaptive immune system; current literature demonstrates the development of serum neutralization in some cases of phage therapy, although the clinical impact seems variable. A summary of current clinical trials involving patients with chronic lung disease is presented, though none are specifically targeting lung transplant candidates or recipients. In addition to treatment of active infections, a variety of clinical scenarios may benefit from phage therapy, and well-designed clinical trials involving this vulnerable patient population are needed: pre- or peritransplantation use of phage in the setting of MDR organism colonization may lead to waitlisting of candidates currently declined by many centers, along with potential reduction of waitlist mortality rates and posttransplant infections; phage may be used for biofilm-related bronchial stent infections; and, finally, there is a possibility that phage use can affect allograft function and chronic rejection.

A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes.

BACKGROUND: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections. METHODS: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded. RESULTS: Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported. CONCLUSIONS: Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.

Therapeutic Potential of Intravenous Phage as Standalone Therapy for Recurrent Drug-Resistant Urinary Tract Infections.

Recurrent urinary tract infections (rUTI) are common in kidney transplant recipients (KTR) and are associated with multidrug resistance and increased morbidity/mortality. Novel antibiotic alternatives to reduce UTI recurrence are critically needed. We describe a case of rUTI due to extended spectrum beta lactamase (ESBL) Klebsiella pneumoniae in a KTR that was treated successfully with 4 weeks of adjunctive intravenous bacteriophage therapy alone, without concomitant antibiotics, and with no recurrence in a year of follow-up.

Study on the impact of exogenously applied methyl jasmonate concentrations on Solanum lycopersicum under low temperature stress.

BACKGROUND: To decipher the capability of Methyl Jasmonate (MeJA) in resisting cold stress in Solanum lycopersicum assessment regarding various physiological parameters in response to diverse doses of MeJA was done. Low temperature (LT) were given to the plants with MeJA (J1C, J2C, J3C) or without MeJA (LT) application. MeJA in the form of foliar spray was given before stress, during stress and after stress. Three concentrations of MeJA were used under normal and LT stress conditions that includes of J1 (0.5 µM), J2 (10 µM), and J3 (15 µM). RESULTS: Oxidative stress, growth characteristics, stress tolerance parameters, antioxidant response and photosynthetic parameters were investigated. In our current study we observed that oxidative stress markers declined by MeJA supplementation under cold stress conditions. MeJA boosted antioxidant enzyme activity along with photosynthetic parameters. The best concentration of MeJA was J2 based on results obtained. This is the first study related to MeJA best dose screening in Solanum lycopersicum under LT stress conditions. CONCLUSION: The LT stress in the Solanum lycopersicum plant was reduced by MeJA. The adverse consequences of LT stress can be significantly attenuated by the J2 concentration of MeJA. So, the optimal concentration of MeJA supplied exogenously to LT stressed Solanum lycopersicum can be a smart strategy to mitigate harmful impact of LT stress on detox system and overall growth of plant.

Post-acute sequelae of COVID-19 in solid organ transplant recipients.

BACKGROUND: Post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), defined as prolonged symptoms following an episode of COVID-19, is not well-characterized in solid organ transplant recipients (SOTR). In this study, we aimed to assess the prevalence of PASC in SOTR, its descriptive characteristics, and associated risk factors. METHODS: We retrospectively identified SOTRs with acute COVID-19 between June 1, 2020 and April 15, 2022, and abstracted demographic and medical history, characteristics of acute COVID-19 illness, and COVID-19 vaccination status. We defined PASC as ongoing/new symptoms present at 6 weeks or longer following acute COVID-19 diagnosis. RESULTS: Among 208 SOTRs with acute COVID-19, 72 (35%) developed PASC. Common symptoms were respiratory symptoms (67%), headache (40%), and difficulty concentrating (10%). Severe acute COVID-19 disease and presence of respiratory symptoms were associated with higher odds of PASC in multivariable analyses, while receipt of at least one COVID-19 vaccination prior to transplantation was protective. CONCLUSION: We found that PASC occurs in about a third of SOTRs with acute COVID-19 and has similar symptoms as described previously in immunocompetent hosts. Pre-transplant vaccination may be protective. Further prospective multicenter studies are needed.

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

Considerations for the Use of Phage Therapy in Clinical Practice.

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, and clinical situations in which phage therapy might be considered. Large gaps in knowledge contribute to heterogeneity in approach and lack of consensus in many important clinical areas. The Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify questions based on a clinical framework and divided them into three themes: potential clinical situations in which phage therapy might be considered, laboratory testing, and pharmacokinetic considerations. Suggestions are provided as answers to a series of questions intended to inform clinicians considering experimental phage therapy for patients in their clinical practices.

Low mortality in SARS-CoV-2 infected heart transplant recipients at a single center.

Immunosuppressed heart transplant (HT) recipients are thought to be at higher risk of infection and mortality from SARS-CoV-2 infection coronavirus disease 2019 (COVID-19); however, evidence guiding management of HT patients are limited. Retrospective search of electronic health records from February 2020 to February 2021, identified 28 HT recipients out of 400 followed by UC San Diego who tested positive for SARS-CoV-2. Patient demographics, COVID-19 directed therapies, hospital course and outcomes were compared to control HT recipients who tested negative for SARS-CoV-2 during the same period (n = 80). Among 28 HT recipients who tested positive for SARS-CoV-2, 15 were admitted to the hospital and 13 were monitored closely as outpatients. Among inpatients, five developed severe illness and two died (7% mortality). Nine patients were treated with remdesivir, and four received dexamethasone and remdesivir. Two outpatients received neutralizing monoclonal antibody therapy and one outpatient received dexamethasone for persistent dyspnea. Immunosuppressed HT recipients, especially Hispanic patients and patients with higher body mass index, were at greater risk of infection and mortality from COVID-19 than the general population. Use of remdesivir and dexamethasone may have improved outcomes in our HT recipients compared to HT recipients at other centers.

Coronavirus disease 2019 vaccination is protective of clinical disease in solid organ transplant recipients.

BACKGROUND: Clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in solid organ transplant recipients (SOTRs) is not well documented despite multiple studies demonstrating sub-optimal immunogenicity. METHODS: We reviewed medical records of eligible SOTRs at a single center to assess vaccination status and identify cases of symptomatic COVID-19 from January 1 to August 12, 2021. We developed a Cox proportional hazards model using the date of vaccination and time since transplantation as a time-varying covariate with age and gender as potential time-invariant confounders. Survival curves were created using the parameters estimated from the Cox model. RESULTS: Among 1904 SOTRs, 1362 were fully vaccinated (96% received mRNA vaccines) and 542 were either unvaccinated (n = 470) or partially vaccinated (n = 72). There were 115 cases of COVID-19, of which 12 occurred in fully vaccinated individuals. Cox regression with the date of vaccination and time since transplantation as the time-varying co-variates showed that after baseline adjustment for age and sex, being fully vaccinated had a significantly lower hazard for COVID-19, hazard ratio (HR) = 0.29 and 95% confidence interval ([CI] 0.09, 0.91). CONCLUSION: We found that 2-dose mRNA COVID-19 vaccination was protective of symptomatic COVID-19 in vaccinated versus unvaccinated SOTRs. TWEET: COVID-19 vaccination was associated with a significantly lower hazard for symptomatic COVID-19 (HR 0.29; 95% CI 0.09, 0.91) among 1904 SOT recipients at a single center from January 1 to August 12, 2021.

Donor-derived tuberculosis among solid organ transplant recipients in the United States-2008 to 2018.

Mycobacterium tuberculosis can be transmitted via organ donation and result in severe outcomes. To better understand donor-derived tuberculosis (DDTB), all potential transmissions reported to the Organ Procurement and Transplantation Network (OPTN) Ad Hoc Disease Transmission Advisory Committee between 2008 and 2018 were analyzed. Among 51 total reports, nine (17%) (9 donors/35 recipients) had ≥ 1 recipient with proven/probable disease transmission. Of these, eight were reported due to recipient disease, and one was reported due to a positive donor result. Proven/probable DDTB transmissions were reported in six lung and five nonlung recipients. The median time to diagnosis was 104 days posttransplant (range 0-165 days). Pulmonary TB, extrapulmonary TB, pulmonary plus extrapulmonary TB, and asymptomatic TB infection with positive interferon-gamma release assay were present in five, three, one, and two recipients, respectively. All recipients received treatment and survived except for one whose death was not attributed to TB. All donors associated with proven/probable DDTB had ≥ 1 TB risk factor. Six were born in a TB-endemic country, five had traveled to a TB-endemic country, three had been incarcerated, and three had latent TB infection. These cases highlight the importance of evaluating donors for TB based on risk factors. Early posttransplant TB in organ recipients of donors with TB risk factors requires prompt reporting to OPTN to identify other potential affected recipients and implement timely treatment interventions.

Role of bacteriophage therapy for resistant infections in transplant recipients.

PURPOSE OF REVIEW: Multidrug-resistant organisms (MDROs) are prevalent in transplant recipients and associated with poor outcomes. We review recent cases of phage therapy used to treat recalcitrant infections in transplant recipients and explore the future role of such therapy in this setting. RECENT FINDINGS: Individual case reports and small case series suggest possible efficacy of phage therapy for the treatment of MDRO infections in pre and posttransplant patients. Importantly, there have been no serious safety concerns in the reported cases that we reviewed. There are no applicable randomized controlled trials (RCTs) to better guide phage therapy at this time. SUMMARY: Given the safety and possibility of successful salvage therapy of MDRO infections using bacteriophages, it is reasonable to pursue phage therapy for difficult-to-treat infections on a compassionate use basis, but RCT data are critically needed to better inform management.

Cost-effectiveness of using hepatitis C viremic hearts for transplantation into HCV-negative recipients.

Outcomes following hepatitis C virus (HCV)-viremic heart transplantation into HCV-negative recipients with HCV treatment are good. We assessed cost-effectiveness between cohorts of transplant recipients willing and unwilling to receive HCV-viremic hearts. Markov model simulated long-term outcomes among HCV-negative patients on the transplant waitlist. We compared costs (2018 USD) and health outcomes (quality-adjusted life-years, QALYs) between cohorts willing to accept any heart and those willing to accept only HCV-negative hearts. We assumed 4.9% HCV-viremic donor prevalence. Patients receiving HCV-viremic hearts were treated, assuming $39 600/treatment with 95% cure. Incremental cost-effectiveness ratios (ICERs) were compared to a $100 000/QALY gained willingness-to-pay threshold. Sensitivity analyses included stratification by blood type or region and potential negative consequences of receipt of HCV-viremic hearts. Compared to accepting only HCV-negative hearts, accepting any heart gained 0.14 life-years and 0.11 QALYs, while increasing costs by $9418/patient. Accepting any heart was cost effective (ICER $85 602/QALY gained). Results were robust to all transplant regions and blood types, except type AB. Accepting any heart remained cost effective provided posttransplant mortality and costs among those receiving HCV-viremic hearts were not >7% higher compared to HCV-negative hearts. Willingness to accept HCV-viremic hearts for transplantation into HCV-negative recipients is cost effective and improves clinical outcomes.