Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C–Viremic Donor to Uninfected Recipient Kidney Transplantation

Abstract

Introduction: Long wait times for kidney transplants have prompted investigation into strategies to decrease the discarding of potentially viable organs. Recent reports suggest that kidneys from hepatitis C virus (HCV)Àinfected donors may be transplanted into HCV-naive donors followed by direct-acting antiviral therapy.Methods: This was a pilot clinical trial to transplant kidneys from HCV-infected donors into HCV-naive recipients with preemptive use of elbasvir and grazoprevir for 12 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy. Secondary outcomes were safety, quality of life, and early viral kinetics.Results: A total of 33 patients were screened, and 8 underwent kidney transplantation from a HCV-viremic donors from August 2017 to March 2019. The median donor kidney donor profile index was 31% (range, 29%À65%), and patients who underwent transplantation waited a median of 6.5 months (range, 1À19 months). None had detectable HCV viremia beyond 2 weeks post-transplantation, and all achieved sustained virologic response 12 weeks after therapy (SVR12). There were no study-related severe adverse events. One patient experienced early graft loss due to venous thrombosis, whereas the remaining 7 patients had excellent allograft function at 6 months. Conclusion:Preemptive elbasvir and grazoprevir eliminated HCV infection in HCV-naive patients who received a kidney transplant from an HCV-infected donor.

Commercial insurance delays direct‐acting antiviral treatment for hepatitis C kidney transplantation into uninfected recipients

“…Similarly, Sise et al demonstrated that prophylactic DAA therapy can shorten the duration of viremia by providing the first dose of a 12‐week DAA course in the operating room. In this cohort, seven of eight patients had detectable viral loads post‐operatively with only one patient remaining detectable after post‐operative day 7 11 …”

“…Published literature has consistently demonstrated near 100% certainty of donor transmission of HCV in the absence of prophylactic DAAs 4 . However, early or prophylactic treatment with DAA has been shown to greatly reduce the incidence of viremia and decrease detectable viral loads 2,9‐11 . Here we examine the effect of the cumbersome authorization processes as it relates to pharmacy benefit plans and the timing of DAA treatment in our cohort of uninfected kidney recipients transplanted with HCV‐positive donor kidneys.…”

Survey of Clinician Opinions on Kidney Transplantation from Hepatitis C Virus Positive Donors: Identifying and Overcoming Barriers

“…Recently, larger case series have confirmed these results. 5,9,12,17,18,[25][26][27][28][29][30][31][32] Despite the published outcomes in clinical studies, the development of safe and effective strategies to utilize DHCV NAT+ organs is challenging. 10 Safe transplantation requires coordination to ensure universal posttransplant testing, access to DAAs for viremic patients, and appropriate monitoring to ensure compliance and viral clearance.…”

“…including groups which achieved high levels of viral clearance with shorter courses of DAA treatment, although several patients required retreatment as a result of viral resistance. 12,[15][16][17][18] Despite this rapidly changing landscape, knowledge and comfort with transplantation of DHCV+ organs has not been systematically assessed. Clinical care and decision-making for transplant providers is more complex for DHCV NAT+ kidneys, due to potential concerns about medical and psychosocial risks for the recipients.…”

Updated View on Kidney Transplant from HCV-Infected Donors and DAAs

“…Regimens provided with safety and efficacy towards all HCV genotypes, even in patients with advanced CKD, should be adopted. Overall, a total of 201 kidney transplants were collected ( Table 3 ); as listed in Table 3 and Table 4 , the majority of the reports had high efficacy and safety [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. However, some studies were externally funded, and this is a source of bias [ 48 ].…”