Liver, simultaneous liver‐kidney, and kidney transplantation from hepatitis C‐positive donors in hepatitis C‐negative recipients: A single‐center study

Abstract

Transplantation of organs from hepatitis C virus (HCV)-antibody (Ab) and -nucleic acid test (NAT) positive donors into HCV-negative recipients has been proposed to expand the donor pool and shorten waiting times. Data on early single-center outcomes are lacking. Nineteen liver (LT, including seven simultaneous liver-kidney [SLKT]) and 17 kidney transplant (KT) recipients received organs from HCV (+) donors; of these, 13 were HCV NAT (+) in each group. All patients who received organs from HCV NAT (+) donors developed HCV viremia post-transplant except for 2 KT recipients. Patients were treated with a variety of direct-acting antiviral regimens, with high rates of sustained virologic response among those with at least 12 weeks of follow-up past the end of treatment: 12/13 (92%) and 8/8 (100%) among LT/SLKT, and KT recipients. Median time to treatment start was 42 days (interquartile range[IQR] 35-118 days) and 40 days (IQR 26-73) post-LT/SLKT and KT, respectively. One death occurred in a SLKT recipient unrelated to HCV or its treatment. There was no significant increase in rejection, proteinuria, or changes in immunosuppression in any group. Organs from HCV-viremic donors can be utilized for HCV-uninfected recipients with good short-term outcomes. K E Y W O R D Shepatitis C virus, hepatitis C-positive donors, kidney transplantation, liver transplantation 2 of 11 | CRISMALE Et AL. unacceptable due to the low efficacy and high risks associated with IFN-based therapy post-transplantation. Such organs were therefore reserved for transplantation into those already with HCV infection. Even among these patients, the persistence of HCV infection post-transplantation was associated with poor outcomes and led to worse post-transplant survival. 4,5 However, the advent of highly effective direct-acting antiviral therapy (DAAs) has led to post-transplantation HCV cure rates exceeding 95%, and with it, a negation of the ill effects of HCV previously seen in both LT and KT recipients. 6,7 A number of clinical trials, along with data from the HCV-TARGET cohort, have demonstrated the efficacy and safety of the use of these agents in the post-transplant setting. 8,9 In the HCV-TARGET cohort, adverse events leading to treatment discontinuation were uncommon, affecting only 1.6%. 8 Newer agents, including glecaprevir/ pibrentasvir (GLE/PIB), have similarly been shown to be safe and efficacious. 10 Indeed, recently published data derived from the Scientific Registry of Transplant Recipients (SRTR) suggest equivalent 1-and3-year survival among HCV-infected patients undergoing LT. 6 In the United States, the potential pool of HCV-positive organs is growing, largely due to a rising incidence of HCV in persons who inject drugs. There is significant geographic and demographic overlap between the opioid epidemic and incident HCV infection. 11 Data suggest that up to 52% of HCV-infected individuals are concentrated in 9 US states, the majority of which have a significant burden of patients suffering with opioid addiction. 12 Drug overdose...

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

“…Third, we assumed in our baseline model that patients who received an HCV‐viremic heart and then successfully achieved SVR would have no negative consequences on further health outcomes. Thus far in early trials, there have been no reports of increased rates of rejection, increased infectious complications, or increased mortality among those receiving HCV‐viremic organs 20‐24,68‐76 . However, these outcomes are early and so in our sensitivity analysis we incrementally increased both costs and mortality to account for this possibility, finding that willingness to accept a heart was cost effective provided it is not associated with a relative increase of more than 7% posttransplant mortality compared to those receiving HCV‐negative hearts.…”

“…We examined the impact of variations in HCV prevalence among organ donors (2.5% or 10% compared to 4.9% at baseline), DAA SVR (90% compared to 95%), and DAA cost ($13 000, $24 000, and $80 000 compared to $39 600), and baseline cohort age (40‐65 years, compared to 50 at baseline). Although early data have not demonstrated significant differences in mortality, graft function, or rejection among recipients of HCV‐viremic compared to HCV‐negative organs, 20‐24,68‐76 we additionally performed a sensitivity analysis to evaluate the potential for negative outcomes in patients receiving hearts from HCV‐viremic donors by incrementally varying the posttransplant mortality and costs in this group by a relative 1%‐10% compared to those receiving HCV‐negative hearts. Finally, we undertook a probabilistic sensitivity analysis where we varied all model input parameters simultaneously using 10 000 simulations to determine uncertainty in the ICER (sampling distributions in Table 1), plotting the proportion of simulations which fell under various WTP thresholds.…”

Use of Organs from Hepatitis C Viremic Donors: Addressing the Needs of a Changing Waitlist and the Effect of a Public Health Crisis

“…Between 2005-2010, livers from donors with hepatitis C were three times more likely to be discarded, but after 2013, this relative risk of discard dropped to 1.7 [18]. These therapies have been utilized in both renal [19][20][21] and thoracic organ transplants [22][23], and in more recent years, larger cohorts have been examined in the liver transplant population [24][25][26].…”

“…That is to say that in the era of DAA therapy, HCV negative recipients have the same graft outcome regardless on the viremic status of their donor. More recently, early experience of favorable outcomes in prospectively analyzed cohorts of patients have begun to be reported [24][25][26].…”

“…There is wide variability amongst transplant centers as to when treatment should be initiated, mainly owing to the fact that payment for the treatments may not be immediately available. Recent data suggests that treatment as soon as five days after transplant is safe and highly effective at preventing HCV infection related complications [24]. Procurement for DAA therapy was obtained via a multi-step process with an institution-supported protocol, complete with a safety-net, underscoring the complexities that come when treating patients so soon after transplant when they may not have positive testing already.…”