To determine the effect of donor hepatitis C virus (HCV) infection on kidney transplant (KT) outcomes in the era of direct-acting antiviral (DAA) medications, we examined 68,087 HCV-negative KT recipients from a deceased donor between March 2015 and May 2021. A Cox regression analysis was used to estimate adjusted hazard ratios (aHRs) of KT failure, incorporating inverse probability of treatment weighting to control for patient selection to receive an HCV-positive kidney (either nucleic acid amplification test positive [NAT+, n = 2331] or antibody positive (Ab+)/NAT- [n = 1826]) based on recipient characteristics. Compared with kidney from HCV-negative donors, those from Ab+/NAT- (aHR = 0.91; 95% confidence interval [CI], 0.75-1.10) and HCV NAT+ (aHR = 0.89; 95% CI, 0.73-1.08) donors were not associated with an increased risk of KT failure over 3 years after transplant. Moreover, HCV NAT+ kidneys were associated with a higher 1-year estimated glomerular filtration (63.0 vs 61.0 mL/min/1.73 m2, P = .007) and lower risk of delayed graft function (aOR = 0.76; 95% CI, 0.68-0.84) compared with HCV-negative kidneys. Our findings suggest that donor HCV positivity is not associated with an elevated risk of graft failure. The inclusion of donor HCV status in the Kidney Donor Risk Index may no longer be appropriate in contemporary practice.

Kidney transplantation is the optimal therapy for end-stage kidney disease but limited by the available number of organs. Using HCV+ donors, both in HCV+ and HCV- recipients, is a rational response to the organ shortage. We review the historic experience using HCV+ donors in HCV+ recipients and assess long-term results. We also discuss contemporary practices, including the transplantation of HCV-viremic kidneys into HCV- recipients with different approaches to posttransplant HCV therapy.

Each hepatitis virus-Hepatitis A, B, C, D, E, and G-poses a distinct scenario to the patient and clinician alike. Since the discovery of each virus, extensive knowledge regarding epidemiology, virologic properties, and the natural clinical and immunologic history of acute and chronic infections has been generated. Basic discoveries about host immunologic responses to acute and chronic viral infections, combined with virologic data, has led to vaccines to prevent Hepatitis A, B, and E and highly efficacious antivirals for Hepatitis B and C. These therapeutic breakthroughs are transforming the fields of hepatology, transplant medicine in general, and public and global health. Most notably, there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade. While attainable, there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local, national, and international scales. Herein, we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.

The discrepancy between the number of potential available kidneys and the number of patients listed for kidney transplant continues to widen all over the world. The transplant of kidneys from hepatitis C virus (HCV)-infected donors into HCV naïve recipients has grown recently because of persistent kidney shortage and the availability of direct-acting antiviral agents. This strategy has the potential to reduce both waiting times for transplant and the risk of mortality in dialysis.

We made an extensive review of the scientific literature in order to review the efficacy and safety of kidney transplant from HCV-viremic donors into HCV naïve recipients who received early antiviral therapy with direct-acting antiviral agents (DAAs).

Evidence has been rapidly accumulated on this topic and some reports have been published (n = 11 studies, n = 201 patients) over the last three years. Various combinations of DAAs were administered-elbasvir/grazoprevir (n = 38), glecaprevir/pibrentasvir (n = 110), and sofosbuvir-based regimens (n = 53). DAAs were initiated in a range between a few hours before renal transplant (RT) to a median of 76 days after RT. The sustained virological response (SVR) rate was between 97.5% and 100%. A few severe adverse events (SAEs) were noted including fibrosing cholestatic hepatitis (n = 3), raised serum aminotransferase levels (n = 11), and acute rejection (n = 7). It remains unclear whether the AEs were related to the transmission of HCV, the use of DAAs, or kidney transplant per se. It appears that the frequency of AEs was greater in those studies where DAAs were not given in the very early post-kidney transplant phase.

The evidence gathered to date encourages the expansion of the kidney donor pool with the adoption of HCV-infected donor organs. We suggest that kidney transplants from HCV-viremic kidneys into HCV-uninfected recipients should be made in the context of research protocols. Many of the studies reported above were externally funded and we need research generating "real-world" evidence. The recent availability of pangenotypic combinations of DAAs, which can be given even in patients with eGFR < 30/min/1.73 m2, will promote the notion that HCV-viremic donors are a significant resource for kidney transplant.

Kidneys from donors with hepatitis C virus (HCV) infection are traditionally considered to be at risk for poorer survival outcomes, as reflected in the kidney donor profile index (KDPI). Modern direct-acting antivirals may modify this risk.

Using United Network for Organ Sharing data, HCV-infected adult first-time kidney transplant recipients from 2014 to 2017 were examined. Graft and patient survival were compared in a propensity-matched cohort of recipients of HCV antibody (Ab)(+) kidneys versus Ab(-) kidneys. Subsequent analysis was performed in a propensity-matched cohort of recipients of HCV-viremic (RNA positive) versus HCV-naïve kidneys.

There were 379 recipients each in the matched cohort of recipients of HCV Ab(+) versus HCV Ab(-) kidneys. Despite a higher KDPI (58.2% for HCV Ab[+] versus 38.8% for HCV Ab[-]), 1-year patient and graft survival were similar in the HCV(+) and HCV(-) groups (95.4% and 94.9% versus 97.9% and 96.0%, P = 0.543 and P = 0.834, respectively). There were 200 recipients each in the cohort of recipients of HCV-viremic versus HCV-naïve kidneys, with the KDPI again higher in the HCV-viremic group (56.8% versus 35.2%). Baseline hazard ratios (HRs) for graft failure (HR, 4.69; P = 0.009) and death (HR, 7.60; P = 0.003) were significantly elevated in the viremic group, but crossed 1 at 21 and 24 months, respectively.

In the modern direct-acting antiviral era, calculated likely KDPI overestimates risk kidneys from HCV (+) donors. Donor viremia conveys an early risk which appears to subside over time. These results suggest that it may be time to revise the kidney donor risk index.

Less than 4% of patients with kidney failure receive kidney transplants. Although discard rates of hepatitis C virus (HCV)-viremic kidneys are declining, ~39% of HCV-viremic kidneys donated between 2018 and 2019 were discarded. Highly effective antiviral agents are now available to treat chronic HCV infection. Thus, our objective was to examine the cost-effectiveness of transplanting kidneys from HCV-viremic donors into HCV-uninfected recipients.

Markov state transition decision model. Data sources include Medline search results, bibliographies from relevant English language articles, Scientific Registry of Transplant Recipients, and the US Renal Data System.

US patients receiving maintenance hemodialysis who are on kidney transplant waiting lists.

Transplantation with an HCV-unexposed kidney versus transplantation with an HCV-viremic kidney and HCV treatment.

Effectiveness measured in quality-adjusted life-years and costs measured in 2018 US dollars.

We used a health care system perspective with a lifelong time horizon.

In the base-case analysis, transplantation with an HCV-viremic kidney was more effective and less costly than transplantation with an HCV-unexposed kidney because of the longer waiting times for HCV-unexposed kidneys, the substantial excess mortality risk while receiving dialysis, and the high efficacy of direct-acting antiviral agents for HCV infection. Transplantation with an HCV-viremic kidney was also preferred in sensitivity analyses of multiple model parameters. The strategy remained cost-effective unless waiting list time for an HCV-viremic kidney exceeded 3.1 years compared with the base-case value of 1.56 year.

Estimates of waiting times for patients willing to accept an HCV-viremic kidney were based on data for patients who received HCV-viremic kidney transplants.

Transplanting kidneys from HCV-viremic donors into HCV-uninfected recipients increased quality-adjusted life expectancy and reduced costs compared with a strategy of transplanting kidneys from HCV-unexposed donors.

Introduction: The introduction of direct-acting antiviral therapy has generated tremendous interest in transplanting organs from HCV-infected donors, an option which has the potential to lower waiting times for solid organ transplantation (including kidneys). Safe, effective and pangenotypic direct-acting antiviral agents are currently available.Areas covered: We have identified studies from PubMed, EMBASE, and the Cochrane database to review risks and benefits on solid organ transplantation from HCV-exposed donors in uninfected recipients.Expert opinion: The transmission of HCV with transplantation from anti-HCV positive kidneys without viremia is extremely uncommon whereas recent evidence (five clinical studies, n = 94 patients) shows the absence of HCV infection in HCV-naïve recipients who received kidneys from HCV RNA-positive donors and underwent early DAAs. The evidence regarding non-kidney solid organ transplantation from HCV-infected donors is more limited. One report showed the occurrence of dialysis-dependent kidney failure due to glomerulonephritis induced by acute HCV after liver transplant from a NAT-positive donor into an HCV-naïve recipient. Transplantation of kidneys and other solid organs from HCV-viremic donors into uninfected recipients has the potential to become the standard of care resulting in lower waitlist mortality. Further studies are needed urgently to establish clinical practice guidelines on this topic.

Due to the unfortunate epidemic of opioid overdose deaths among people who inject drugs (PWID) in North America, there has been an increase in the availability of hepatitis C (HCV)-positive organs for transplantation and consequently the potential to decrease waiting times for solid organ transplantation if an HCV-uninfected recipient is willing to accept an HCV-positive donor. The confidence in this potential new strategy comes as a result of the advent of safe and highly effective pan-genotypic direct-acting antivirals (DAAs). This promising strategy has been the most widely studied in kidney transplantation. Liver transplantation has positive results preliminarily, but has even less available data because viable HCV-infected donor livers are typically transplanted into HCV-infected individuals. Further, while HCV-infected heart and lung transplantation, which face additional post-transplant issues, have shown encouraging results, these studies are small scale and are limited by short-term follow-up. Thus, it would be premature to implement this strategy as standard of care without large scale clinical and real-world trials and longer-term follow-up studies. Further, the ethics of this practice need to be considered. While some transplant professionals argue that more harm will be done by not utilizing HCV-infected organs, others contend that cautiously conducted multi-centre studies involving extensive post-transplant follow-up are paramount prior to endorsing widespread implementation of this strategy. The ethical permissibility of this practice hinges on whether access to DAA therapy can be secured in advance, and prospective recipients understand and accept all the risks associated with acquiring HCV.

Hepatitis C (HCV) is a worldwide health problem. Effective therapies for HCV infection, coupled with an increase in deceased donors due to the opioid epidemic, have led to the broader availability and the use of HCV-infected donor organs, including HCV nucleic acid test-positive (NAT+) donors in HCV-negative recipients. In this review, we discuss the prevalence of HCV infection, trends in the use of HCV-infected donors, and outcomes for those who receive HCV-seropositive or HCV NAT+ donor organs. We discuss management considerations such as hepatitis B reactivation, selection of the optimal direct-acting antiviral regimen, and potential complications. We also present a framework for the rational use of HCV-infected donor organs in the future.

The availability of direct-acting antiviral (DAA) therapy might have impacted use of hepatitis C virus (HCV)-infected (HCV+) deceased donor kidneys for transplantation.

We used 2005 to 2018 Scientific Registry of Transplant Recipients data to identify 18 936 candidates willing to accept HCV+ kidneys and 3348 HCV+ recipients of HCV+ kidneys. We compared willingness to accept, utilization, discard, and posttransplant outcomes associated with HCV+ kidneys between 2 treatment eras (interferon [IFN] era, January 1, 2005 to December 5, 2013 vs DAA era, December 6, 2013 to August 2, 2018). Models were adjusted for candidate, recipient, and donor factors where appropriate.

In the DAA era, candidates were 2.2 times more likely to list as willing to accept HCV+ kidneys (adjusted odds ratio, 2.072.232.41; P < 0.001), and HCV+ recipients were 1.95 times more likely to have received an HCV+ kidney (adjusted odds ratio, 1.761.952.16; P < 0.001). Median Kidney Donor Profile Index of HCV+ kidneys decreased from 77 (interquartile range [IQR], 59-90) in 2005 to 53 (IQR, 40-67) in 2017. Kidney Donor Profile Index of HCV- kidneys remained unchanged from 45 (IQR, 21-74) to 47 (IQR, 24-73). After adjustment, HCV+ kidneys were 3.7 times more likely to be discarded than HCV- kidneys in the DAA era (adjusted relative rate, 3.363.674.02; P < 0.001); an increase from the IFN era (adjusted relative rate, 2.783.023.27; P < 0.001). HCV+ kidney use was concentrated within a subset of centers; 22.5% of centers performed 75% of all HCV+ kidney transplants in the DAA era. Mortality risk associated with HCV+ kidneys remained unchanged (aHR, 1.071.191.32 in both eras).

Given the elevated risk of death on dialysis facing HCV+ candidates, improving quality of HCV+ kidneys, and DAA availability, broader utilization of HCV+ kidneys is warranted to improve access in this era of organ shortage.

Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus.

Retrospective cohort study.

Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014.

HCV antibody serostatus obtained as part of clinical data from a national dialysis provider.

Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist.

After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals.

Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney.

No data for HCV viral load or liver biopsy.

HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct-acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart-kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.

Kidney transplant from donors with hepatitis C virus (HCV) antibody has been limited to HCV viremic recipients only, due to concern of the HCV transmission. However, the new antiviral medications provide an opportunity to expand the utilization of these donors. To study the risk of HCV transmission in kidney transplantation, we used discarded donor kidneys and determined HCV RNA levels by quantitative real-time PCR in bilateral (right and left) kidney biopsies and plasma from 14 HCV antibody-positive donors (sensitivity: 15 international unit (IU)/mL plasma; 1.8 IU/50 nL kidney). In three NAT-negative donors, HCV RNA was negative in plasma and kidney. In all 11 NAT-positive donors, HCV RNA was positive in plasma (range: 5807-19 134 177 IU/mL) but negative in six kidneys from four donors with plasma HCV RNA <1.5 million IU/μL. HCV RNA correlated between right and left kidneys (P = 0.75) and between kidney and plasma (r = 0.86). When normalized by volume, HCV RNA median (range) was 49 (0-957) IU/50 nL plasma and 1.0 (0-103) IU/50 nL kidney, significantly lower in kidney (P = 0.005) than in plasma (14-fold). Plasma HCV RNA can be used to predict the kidney HCV load. Future studies are needed if plasma/kidney HCV levels can be used to stratify donors for transmission risk and recipients for post-transplant management in extended utilization of HCV antibody-positive donors.

Direct-acting antiviral agents are now available to treat chronic hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD).

To examine whether it is more cost-effective to transplant HCV-infected or HCV-uninfected kidneys into HCV-infected patients.

Markov state-transition decision model.

MEDLINE searches and bibliographies from relevant English-language articles.

HCV-infected patients with ESRD receiving hemodialysis in the United States.

Lifetime.

Health care system.

Transplant of an HCV-infected kidney followed by HCV treatment versus transplant of an HCV-uninfected kidney preceded by HCV treatment.

Effectiveness, measured in quality-adjusted life-years (QALYs), and costs, measured in 2017 U.S. dollars.

Transplant of an HCV-infected kidney followed by HCV treatment was more effective and less costly than transplant of an HCV-uninfected kidney preceded by HCV treatment, largely because of longer wait times for uninfected kidneys. A typical 57.8-year-old patient receiving hemodialysis would gain an average of 0.50 QALY at a lifetime cost savings of $41 591.

Transplant of an HCV-infected kidney followed by HCV treatment continued to be preferred in sensitivity analyses of many model parameters. Transplant of an HCV-uninfected kidney preceded by HCV treatment was not preferred unless the additional wait time for an uninfected kidney was less than 161 days.

The study did not consider the benefit of decreased HCV transmission from treating HCV-infected patients.

Transplanting HCV-infected kidneys into HCV-infected patients increased quality-adjusted life expectancy and reduced costs compared with transplanting HCV-uninfected kidneys into HCV-infected patients.

Merck Sharp & Dohme and the National Center for Advancing Translational Sciences.

The epidemic of drug overdose deaths in the United States has led to an increase in organ donors.

To characterize donors who died of overdose and to analyze outcomes among transplant recipients.

Prospective observational cohort study.

Scientific Registry of Transplant Recipients, 1 January 2000 to 1 September 2017.

138 565 deceased donors; 337 934 transplant recipients at 297 transplant centers.

The primary exposure was donor mechanism of death (overdose-death donor [ODD], trauma-death donor [TDD], or medical-death donor [MDD]). Patient and graft survival and organ discard (organ recovered but not transplanted) were compared using propensity score-weighted standardized risk differences (sRDs).

A total of 7313 ODDs and 19 897 ODD transplants (10 347 kidneys, 5707 livers, 2471 hearts, and 1372 lungs) were identified. Overdose-death donors accounted for 1.1% of donors in 2000 and 13.4% in 2017. They were more likely to be white (85.1%), aged 21 to 40 years (66.3%), infected with hepatitis C virus (HCV) (18.3%), and increased-infectious risk donors (IRDs) (56.4%). Standardized 5-year patient survival was similar for ODD organ recipients compared with TDD organ recipients (sRDs ranged from 3.1% lower to 3.9% higher survival) and MDD organ recipients (sRDs ranged from 2.1% to 5.2% higher survival). Standardized 5-year graft survival was similar between ODD and TDD grafts (minimal difference for kidneys and lungs, marginally lower [sRD, -3.2%] for livers, and marginally higher [sRD, 1.9%] for hearts). Kidney discard was higher for ODDs than TDDs (sRD, 5.2%) or MDDs (sRD, 1.5%); standardization for HCV and IRD status attenuated this difference.

Inability to distinguish between opioid and nonopioid overdoses.

In the United States, transplantation with ODD organs has increased dramatically, with noninferior outcomes in transplant recipients. Concerns about IRD behaviors and hepatitis C among donors lead to excess discard that should be minimized given the current organ shortage.

National Institutes of Health.