The Immune Tolerance Network ITN030ST A‐WISH assessed immunosuppression withdrawal in liver transplant recipients with hepatitis C or nonimmune nonviral liver disease. Of 275 recipients enrolled ...before transplantation, 95 were randomly assigned 4:1 to withdrawal (n = 77) or maintenance (n = 18) 1‐ to 2‐years posttransplant. Randomization eligibility criteria included stable immunosuppression monotherapy; adequate liver and kidney function; ≤Stage 2 Ishak fibrosis; and absence of rejection on biopsy. Immunosuppression withdrawal followed an 8‐step reduction algorithm with ≥8 weeks per level. Fifty‐two of 77 subjects (67.5%) reduced to ≤50% of baseline dose, and 10 of 77 (13.0%) discontinued all immunosuppression for ≥1 year. Acute rejection and/or abnormal liver tests were treated with increased immunosuppression; 5 of 32 rejection episodes required a methylprednisolone bolus. The composite end point (death or graft loss; grade 4 secondary malignancy or opportunistic infection; Ishak stage ≥3; or >25% decrease in glomerular filtration rate within 24 months of randomization) occurred in 12 of 66 (18%) and 4 of 13 (31%) subjects in the withdrawal and maintenance groups. Early immunosuppression minimization is feasible in selected liver recipients, while complete withdrawal is successful in only a small proportion. The composite end point comparison was inconclusive for noninferiority of the withdrawal to the maintenance group.
The ITN030ST A‐WISH immunosuppression withdrawal study demonstrates that early posttransplantation immunosuppressant minimization is feasible but complete withdrawal is rarely successful.
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The article presents modern ideas about the impact of viral hepatitis C on the course of pregnancy, the severity of maternal disease associated with it: methods of delivery and possible vertical ...transmission. Epidemiological data on the prevalence in the world and the Russian Federation, risk factors for perinatal HCV transmission, and the course of pregnancy in women infected with HCV are shown. The search for the necessary literary sources was carried out in the databases Scopus, PubMed, MedLine, The Cochrane Library, RSCI.
Liver transplantation (LT) from donors‐with‐HIV to recipients‐with‐HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single‐case reports of HIV D+/R+ LT, each with ...limited follow‐up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors‐without‐HIV to recipients‐with‐HIV (HIV D−/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016–July 2019, there were 45 LTs (8 simultaneous liver‐kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D−/R+ (10 D− were false‐positive). The median follow‐up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)‐seropositive, 13% HCV‐viremic. Weighted 1‐year survival was 83.3% versus 100.0% in D+ versus D− groups (p = .04). There were no differences in one‐year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.
A multicenter study of HIV+ donor to HIV+ recipient liver transplantation under the HOPE Act shows that patient and graft survival were better than historical cohorts, but the possible increased incidence of infections and cancer merits further investigation.
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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.
This single‐center study demonstrates the absence of HCV transmission when transplanting kidneys from HCV antibody positive/nucleic acid testing negative donors. See Goldberg and Wolfe's editorial on page 2380.
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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.
This article summarizes key points from a recent multidisciplinary meeting addressing the expansion of transplanting hepatitis C virus–infected donor organs in solid organ recipients. Fishman and Forns respond in an editorial on page 2755, and the conversation continues in the Letters to the Editor section (pages 2986, 2988, 2989).
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Pilot studies suggest that transplanting hepatitis C virus (HCV)–positive donor (D+) kidneys into HCV‐negative renal transplant (RT) recipients (R−), then treating HCV with direct‐acting antivirals ...(DAA) is clinically feasible. To determine whether this is a cost‐effective approach, a decision tree model was developed to analyze costs and effectiveness over a 5‐year time frame between 2 choices: RT using a D+/R− strategy compared to continuing dialysis and waiting for a HCV‐negative donor (D−/R−). The strategy of accepting a HCV+ organ then treating HCV was slightly more effective and substantially less expensive and resulted in an expected 4.8 years of life (YOL) with a cost of ≈$138 000 compared to an expected 4.7 YOL with a cost of ≈$329 000 for the D−/R− strategy. The D+/R− strategy remained dominant after sensitivity analyses including the difference in RT death probabilities or acute rejection probabilities between using D+ vs D− kidney; time that D−/R− patients waited for RT; dialysis death probabilities while waitlisted for RT in the D−/R− strategy; DAA therapy expected cure rate; costs of transplant, immunosuppressives, DAA therapy, dialysis, or acute rejection. The D+/R− strategy followed by treatment with DAA is less costly and slightly more effective compared to the D−/R− strategy.
This cost‐effectiveness analysis using data derived from US Medicare costs and national US waitlist and posttransplant mortality rates suggests that a strategy utilizing HCV nucleic acid test (NAT)‐positive donor kidneys for HCV NAT‐negative recipients followed by HCV treatment is significantly less costly and slightly more effective compared to waiting for HCV NAT‐negative donor kidneys.
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The long‐term safety of heart transplants from hepatitis C viremic (NAT+) donors remains uncertain. We conducted a prospective study of all patients who underwent heart transplantation at our center ...from January 2018 through August 2020. Routine testing was performed to assess for donor‐derived cell‐free DNA, acute cellular rejection (ACR), antibody‐mediated rejection (AMR), and cardiac allograft vasculopathy (CAV). Allograft dysfunction and mortality were also monitored. Seventy‐five NAT− recipients and 32 NAT+ recipients were enrolled in the study. All NAT+ recipients developed viremia detected by PCR, were treated with glecaprevir/pibrentasvir at the time of viremia detection, and cleared the virus by 59 days post‐transplant. Patients who underwent NAT testing starting on post‐operative day 7 (NAT+ Group 1) had significantly higher viral loads and were viremic for a longer period compared with patients tested on post‐operative day 1 (NAT+ Group 2). Through 3.5 years of follow‐up, there were no statistically significant differences in timing, severity, or frequency of ACR in NAT+ recipients compared with the NAT− cohort, nor were there differences in noninvasive measures of graft injury, incidence or severity of CAV, graft dysfunction, or mortality. There were five episodes of AMR, all in the NAT− group. There were no statistically significant differences between Group 1 and Group 2 NAT+ cohorts. Overall, these findings underscore the safety of heart transplantation from NAT+ donors.
A prospective study comparing patients who received heart transplants from hepatitis C viremic and non‐viremic donors finds no differences in acute or chronic rejection, graft dysfunction or mortality.
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The United States opioid use epidemic over the past decade has coincided with an increase in hepatitis C virus (HCV) positive donors. Using propensity score matching, and the Organ Procurement ...Transplant Network data files from January 2015 to June 2019, we analyzed the short‐term outcomes of adult deceased donor kidney transplants of HCV uninfected recipients with two distinct groups of HCV positive donors (HCV seropositive, nonviremic n = 352 and viremic n = 196) compared to those performed using HCV uninfected donors (n = 36 934). Compared to the reference group, the transplants performed using HCV seropositive, nonviremic and viremic donors experienced a lower proportion of delayed graft function (35.2 vs 18.9%; P < .001 HCV seropositive, nonviremic donors and 36.2 vs 16.8% ; P < .001HCV viremic donors). The recipients of HCV viremic donors had better allograft function at 6 months posttransplant (eGFR 54.1 vs 68.3 mL/min/1.73 m2; P = .004. Furthermore, there was no statistical difference in the overall graft failure risk at 12 months posttransplant by propensity score matched multivariable Cox proportional analysis (HR = 0.60, 95% CI 0.23 to 1.29 HCV seropositive, nonviremic donors and HR = 0.85, 95% CI 0.25 to 2.96 HCV viremic donors). Further studies are required to determine the long‐term outcomes of these transplants and address unanswered questions regarding the use of HCV viremic donors.
Using propensity score matching and Organ Procurement Transplantation Network data files, the authors present the short‐term outcomes of adult deceased donor kidney transplants of HCV uninfected recipients with two distinct group of HCV‐positive donors (HCV seropositive, nonviremic and viremic) compared to those using HCV uninfected donors.
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This editorial highlights key practical, clinical, and ethical lessons revealed in Molnar et al's (page 3046) real‐world experience using hepatitis C–infected donor kidneys for uninfected transplant ...recipients universally at a US transplant center as standard practice.
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