Optimal timing of hepatitis C treatment among HIV/HCV coinfected ESRD patients: Pre‐ vs posttransplant

Patients with end‐stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV‐infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney‐only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre‐ and posttransplant, were compared using Monte Carlo microsimulation of 1 000 000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait‐time over a lifetime time horizon. Treatment posttransplant was consistently cost‐saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0‐F1), treatment posttransplant also yielded higher life months (LM) and quality‐adjusted life months (QALM), except among F1 candidates with wait times ≥ 18 months. For candidates with advanced liver disease (F2‐F4), treatment pretransplant afforded more LM and QALM unless wait time was <18 months. Moreover, treatment pretransplant was cost‐effective for F2 candidates with wait times >71 months and F3 candidates with wait times >18 months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely.     

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.     

Cost‐effectiveness of using kidneys from hepatitis C nucleic acid test–positive donors for transplantation in hepatitis C–negative recipients

Kidneys from deceased donors who are hepatitis C virus (HCV) nucleic acid test positive are infrequently used for transplantation in HCV‐negative patients due to concerns about disease transmission. With the development of direct‐acting antivirals (DAAs) for HCV, there is now potential to use these kidneys in HCV‐negative candidates. However, the high cost of DAAs poses a challenge to adoption of this strategy. We created a Markov model to examine the cost‐effectiveness of using deceased donors infected with HCV for kidney transplantation in uninfected waitlist candidates. In the primary analysis, this strategy was cost saving and improved health outcomes compared to remaining on the waitlist for an additional 2 or more years to receive a HCV‐negative transplant. The strategy was also cost‐effective with an incremental cost‐effectiveness ratio of $56 018 per quality‐adjusted life year (QALY) from the payer perspective, and $4647 per QALY from the societal perspective, compared to remaining on the waitlist for 1 additional year. The results were consistent in 1‐way and probabilistic sensitivity analyses. We conclude that the use of kidneys from deceased donors with HCV infection is likely to lead to improved clinical outcomes at reduced cost for HCV‐negative transplant candidates.     

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.     

Early emergence of anti‐HCV antibody implicates donor origin in recipients of an HCV‐infected organ

Hepatitis C virus (HCV) seroconversion among HCV‐uninfected transplant recipients from HCV‐infected (NAT+/Antibody+) or HCV‐exposed (NAT?/Antibody+) donors has been reported. However, the origin of anti‐HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV‐uninfected kidney (n = 31) or heart transplant recipients (n = 9) of an HCV NAT+ organ for anti‐HCV antibody (both IgG and IgM isotypes). Almost half of all participants had detectable anti‐HCV antibody at any point during follow‐up. The majority of antibody‐positive individuals became positive within 1‐3 days of transplantation, and 6 recipients had detectable antibody on the first day posttransplant. Notably, all anti‐HCV antibody was IgG, even in samples collected posttransplant day 1. Late seroconversion was uncommon (≈20%‐25% of antibody+ recipients). Early antibody persisted over 30 days in kidney recipients, whereas early antibody dropped below detection in 50% of heart recipients within 2 weeks after transplant. Anti‐HCV antibody is common in HCV‐uninfected recipients of an HCV NAT+ organ. The IgG isotype of this antibody and the kinetics of its appearance and durability suggest that anti‐HCV antibody is donor derived and is likely produced by a cellular source. Our data suggest that transfer of donor humoral immunity to a recipient may be much more common than previously appreciated.     

Cost‐effectiveness of hepatitis C–positive donor kidney transplantation for hepatitis C–negative recipients with concomitant direct‐acting antiviral therapy

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.     

Cost‐effectiveness analysis of antiviral treatment in liver transplant recipients with HCV infection

Within 5–10 years, 20–40% of hepatitis C virus (HCV)‐infected liver transplant recipients can be expected to develop cirrhosis. Here, cost‐effectiveness of antiviral therapy was assessed. A Markov model was developed to simulate disease progression and calculate outcome and costs of treatment. In the baseline analysis, Peg‐IFN/RBV treatment prevented organ loss/death, gained quality‐adjusted life‐years (QALYs) and undercut the limit of cost‐effectiveness of €50 000/QALY with an incremental cost‐effectiveness ratio of approximately €40 400/QALY and €21 000/QALY for HCV genotype 1 and 2/3 patients, respectively. Furthermore, sensitivity analysis testing modified model parameters according to extreme data described in the literature confirmed cost‐effectiveness for a lower or higher rate of fibrosis progression, increased non‐HCV‐related mortality, lower limits of utilities, a time horizon of 30 years, and additional costs in the year of death. On the other hand, cost‐effectiveness was lost for patients with genotype 1 in case of doubled antiviral or life‐time costs or an increased discount rate of 7%. New treatment strategies for HCV genotype 1 infected patients remained on the same level cost‐effective, if additional costs did not exceed €10 774 per 10% sustained virologic response gain. We conclude that Peg‐IFN/RBV treatment is cost‐effective post transplant. This may support treatment decision in individual cases.     

Toll‐Like Receptor 3 and 7/8 Function Is Impaired in Hepatitis C Rapid Fibrosis Progression Post‐Liver Transplantation

Recurrence of hepatitis C (HCV) postliver transplant is universal, with a subgroup developing rapid hepatic fibrosis. Toll‐like receptors (TLRs) are critical to innate antiviral responses and HCV alters TLR function to evade immune clearance. Whether TLRs play a role in rapid HCV recurrence posttransplant is unknown. We stimulated peripheral blood mononuclear cells (PBMCs) from 70 patients with HCV postliver transplant with TLR subclass‐specific ligands and measured cytokine production, TLR expression and NK cell function. Rate of fibrosis progression was calculated using posttransplant liver biopsies graded by Metavir scoring (F0–4; R = fibrosis stage/year posttransplant; rapid fibrosis defined as >0.4 units/year). Thirty of 70 (43%) patients had rapid fibrosis progression. PBMCs from HCV rapid‐fibrosers produced less IFNα with TLR7/8 stimulation (p = 0.039), less IL‐6 at baseline (p = 0.027) and with TLR3 stimulation (p = 0.008) and had lower TLR3‐mediated monocyte IL‐6 production (p = 0.028) compared with HCV slow fibrosers. TLR7/8‐mediated NKCD56 dim cell secretion of IFNγ was impaired in HCV rapid fibrosis (p = 0.006) independently of IFNα secretion and TLR7/8 expression, while cytotoxicity remained preserved. Impaired TLR3 and TLR7/8‐mediated cytokine responses may contribute to aggressive HCV recurrence postliver transplantation through impaired immune control of HCV and subsequent activation of fibrogenesis.     

Hepatitis C virus genotyping of organ donor samples to aid in transplantation of HCV‐positive organs

Given the availability of new highly efficacious anti‐HCV therapies, some clinicians have advocated for wider use of kidneys from hepatitis C virus‐positive (HCV+) donors, including transplanting them into HCV‐negative recipients. As treatment regimens for HCV are commonly guided by genotype, pretransplant HCV genotyping of tissue donors would be beneficial. To our knowledge, donor HCV genotyping has never been reported. We retrieved archived frozen plasma samples for 17 previous organ donors through a local organ procurement organization. We performed HCV genotyping using the eSensor HCVg Direct Test (GenMark Diagnostics) and also by Sanger sequencing, for confirmation (Retrogen). In addition, viral loads were measured using the COBAS AmpliPrep/TaqMan system (Roche Diagnostics). We found that most of the samples (n = 14) were HCV Genotype 1a with the remainder being Genotype 2b (n = 1) or Genotype 3 (n = 2). All genotyping results were concordant with Sanger sequencing. The average HCV viral load in the sample group was ~ 1.6 million IU/mL (range: ~16 000 IU/mL to 7 million IU/mL). We demonstrate that viral RNA from organ donor plasma can be successfully genotyped for HCV. This ability suggests that transplantation of HCV+ kidneys into HCV‐negative recipients, followed by genotype‐guided antiviral therapy, could be feasible.     

Ultra‐short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

We conducted an adaptive design single‐center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra‐short‐term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)‐nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R?). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12‐week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first‐line DAA therapy; and two after retreatment with second‐line DAA). At a median follow‐up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4‐day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%‐20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R ? transplants.     

Economic Impacts of ABO‐Incompatible Live Donor Kidney Transplantation: A National Study of Medicare‐Insured Recipients

The infrequent use of ABO‐incompatible (ABOi) kidney transplantation in the United States may reflect concern about the costs of necessary preconditioning and posttransplant care. Medicare data for 26 500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2‐incompatible (A2i) recipients, were analyzed to assess the impact of pretransplant, transplant episode and 3‐year posttransplant costs. The marginal costs of ABOi and A2i versus ABO‐compatible (ABOc) transplants were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient survival (93.2% vs. 88.15%, p = 0.0009) and death‐censored graft survival (85.4% vs. 76.1%, p < 0.05) at 3 years were lower after ABOi transplant. The average overall cost of the transplant episode was significantly higher for ABOi ($65 080) compared with A2i ($36 752) and ABOc ($32 039) transplantation (p < 0.001), excluding organ acquisition. ABOi transplant was associated with high adjusted posttransplant spending (marginal costs compared to ABOc ‐ year 1: $25 044; year 2: $10 496; year 3: $7307; p < 0.01). ABOi transplantation provides a clinically effective method to expand access to transplantation. Although more expensive, the modest increases in total spending are easily justified by avoiding long‐term dialysis and its associated morbidity and cost.     

An economic assessment of contemporary kidney transplant practice

Kidney transplantation is the optimal therapy for end‐stage renal disease, prolonging survival and reducing spending. Prior economic analyses of kidney transplantation, using Markov models, have generally assumed compatible, low‐risk donors. The economic implications of transplantation with high Kidney Donor Profile Index (KDPI) deceased donors, ABO incompatible living donors, and HLA incompatible living donors have not been assessed. The costs of transplantation and dialysis were compared with the use of discrete event simulation over a 10‐year period, with data from the United States Renal Data System, University HealthSystem Consortium, and literature review. Graft failure rates and expenditures were adjusted for donor characteristics. All transplantation options were associated with improved survival compared with dialysis (transplantation: 5.20‐6.34 quality‐adjusted life‐years [QALYs] vs dialysis: 4.03 QALYs). Living donor and low‐KDPI deceased donor transplantations were cost‐saving compared with dialysis, while transplantations using high‐KDPI deceased donor, ABO‐incompatible or HLA‐incompatible living donors were cost‐effective (<$100 000 per QALY). Predicted costs per QALY range from $39 939 for HLA‐compatible living donor transplantation to $80 486 for HLA‐incompatible donors compared with $72 476 for dialysis. In conclusion, kidney transplantation is cost‐effective across all donor types despite higher costs for marginal organs and innovative living donor practices.     

Underutilization of Hepatitis C‐Positive Kidneys for Hepatitis C‐Positive Recipients

Hepatitis C‐positive (HCV(+)) candidates likely derive survival benefit from transplantation with HCV(+) kidneys, yet evidence remains inconclusive. We hypothesized that lack of good survival benefit data has led to wide practice variation. Our goal was to characterize national utilization of HCV(+) kidneys for HCV(+) recipients, and to quantify the risks/benefits of this practice. Of 93,825 deceased donors between 1995 and 2009, HCV(+) kidneys were 2.60‐times more likely to be discarded (p < 0.001). However, of 6830 HCV(+) recipients, only 29% received HCV(+) kidneys. Patients over 60 relative rate (RR 0.86), women (RR 0.73) and highly sensitized patients (RR 0.42) were less likely to receive HCV(+) kidneys, while African Americans (RR 1.56), diabetics (RR 1.29) and those at centers with long waiting times (RR 1.19) were more likely to receive them. HCV(+) recipients of HCV(+) kidneys waited 310 days less than the average waiting time at their center, and 395 days less than their counterparts at the same center who waited for HCV(?) kidneys, likely offsetting the slightly higher patient (HR 1.29) and graft loss (HR 1.18) associated with HCV(+) kidneys. A better understanding of the risks and benefits of transplanting HCV(+) recipients with HCV(+) kidneys will hopefully improve utilization of these kidneys in an evidence‐based manner.     

Short‐term outcomes of deceased donor renal transplants of HCV uninfected recipients from HCV seropositive nonviremic donors and viremic donors in the era of direct‐acting antivirals

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 < .001[HCV 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.     

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.     

Use of direct‐acting agents for hepatitis C virus‐positive kidney transplant candidates and kidney transplant recipients

In some parts of the world, hepatitis C virus (HCV) infection remains a huge problem for kidney transplant candidates and kidney transplant (KT) recipients. Until 2 years ago, anti‐HCV treatment for the general population relied on pegylated alpha‐interferon plus ribavirin, but led to a sustained viral response (SVR) in <50% of cases. This treatment was contraindicated in KT patients because of acute‐rejection issues and was poorly tolerated in patients with end‐stage renal disease (ESRD). Over the last year, direct‐acting antiviral agents (DAAs) have entered the market and are associated in the general population with a SVR of >90%, whatever the patient's HCV genotype. In KT patients, sofosbuvir‐based therapy is associated with a SVR at nearly 100% in patients with a HCV genotype‐1 infection, with almost no side effects and only mild interference with immunosuppressive drugs. Most HCV(+) patients with ESRD are genotype 1: in that setting, a recent study reported that the association of grazoprevir/elbasvir 100/50 mg/day led to a SVR of nearly 95% with very few side effects. Thus, it is concluded that DAAs can be safely used and lead to results in KT candidates and KT patients that are as good as those observed in the nonrenal population.     

Real‐world data on healthcare resource consumption and costs before and after kidney transplantation

End‐stage renal disease (ESRD) is increasing worldwide as a consequence of population aging and increasing chronic illness. Treatment consists mostly of dialysis and kidney transplantation (KTx), and KTx offers advantages for life expectancy and long‐term cost reductions compared with dialysis. This study uses the administrative database of the Lombardy Region to analyze the costs of a cohort of patients with ESRD receiving KTx, covering a time period of 24 months before transplant to 12 months after. During 2011, 276 patients underwent kidney transplantation (8.7% preemptive and 91.3% non‐preemptive). In the period before transplantation, the main cost driver was dialysis (66.6% for the period from ?24 to ?12 months and 73.8% for the period from ?12 to 0 months), while in the 12 months after KTx, the most relevant cost was surgery. The total cost ?24 to ?12 months pre‐KTx was 35 049.2€; the cost ?12 to 0 months was 36 745.9€; and the cost 12 months after KTx was 43 805.8€. Non‐preemptive patients showed much higher costs both pre‐ and post‐KTx than preemptive patients. This study highlights how KTx modifies the resource consumption and costs composition of patients with ESRD vs those undergoing dialysis treatment and how KTx may be economically beneficial, especially preemptive intervention.     

The road map toward an hepatitis C virus‐free transplant population

Antiviral therapy to eradicate hepatitis C virus (HCV) infection improves outcomes in patients undergoing liver transplantation (LT) for advanced chronic HCV with or without hepatocellular carcinoma. Traditionally, antiviral therapy focused on the use of interferon (IFN)‐based regimens, with antiviral treatment initiated in the posttransplant period once recurrent HCV disease with fibrosis in the allograft was identified. The use of IFN‐based therapy was limited in pretransplant patients with advanced liver disease. Earlier intervention, either before transplantation or early after LT, is now feasible with the advent of second‐generation direct‐acting antiviral agents (DAAs) with superior tolerability and efficacy to IFN‐based therapy. These agents have the potential to reduce the number of patients developing HCV‐related complications requiring LT and retransplantation, as well as reducing the demand for donor organs. We discuss the pros and cons of pretransplant, peritransplant, and posttransplant therapy with current DAAs, citing available data from clinical trials and real‐world experience.     

Hepatitis C virus infection in end‐stage renal disease and kidney transplantation

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end‐stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV‐positive/ESRD and HCV‐positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct‐acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV‐negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV‐related liver disease.     

Transplantation of kidneys from hepatitis C–infected donors to hepatitis C–negative recipients: Single center experience

Our aim was to evaluate the safety of transplanting kidneys from HCV‐infected donors in HCV‐uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor‐specific antibodies and renal histology. Treatment with a direct‐acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68‐88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA–negative and achieved 12‐week sustained virologic response. The estimated GFRs at end of treatment and 12‐week posttreatment were 67 ± 21 mL/min/1.73 m² and 67 ± 17 mL/min/1.73 m², respectively. Four recipients developed acute rejection. Kidney transplantation from HCV‐infected donors to HCV‐negative recipients should be considered in all eligible patients.