51成人动漫

Antiviral therapy for heart transplant patients begun prior to receiving organs from hepatitis C virus (HCV) infected donors resulted in timelier transplantation, rapid viral suppression, and excellent early allograft function, interim results of an open-label study showed.

But while the regimen prevented chronic HCV infection in non-infected recipients, the long-term outcomes of such transplants remain unknown, researchers reported in .

In 20 recipients of HCV-positive hearts, glecaprevir-pibrentasvir (Mavyret) treatment resulted in a median time to viral clearance of 3.5 days, with all patients achieving sustained viral response (SVR) by week 12, according to Raymond T. Chung, MD, of Massachusetts General Hospital in Boston, and colleagues.

"The use of HCV-infected donor hearts coupled with pre-emptive antiviral therapy should be considered to maximise use of the donor pool and to reduce the morbidity, mortality, and costs associated with end-stage heart failure," the investigators concluded.

According to Chung and associates, glecaprevir-pibrentasvir (whose manufacturer did not fund the study) might be better suited than other direct-acting antiviral agents (DAAs) for heart transplants since it avoids the potentially serious drug- interactions observed with sofosbuvir-based therapy. It might also better suit recipients of other organs from HCV-positive donors because it is pangenotypic, can be given pre-emptively, and can be used in patients with severely impaired kidney function.

The authors noted that each year as many as otherwise suitable for transplantation are estimated to be discarded in the U.S. on the basis of HCV-positivity. In the wake of the opioid crisis, people who die from overdoses are now the fastest-growing organ donor group, and this population has a particularly high prevalence of they explained. "DAAs have provided a unique opportunity to use HCV-positive organs and viably offer life-saving transplantation to uninfected recipients," they wrote.

Study details

The open-label, proof-of-concept study recruited 55 patients from Massachusetts General Hospital Transplant Center over a 13-month period ending in November 2018. Of these, 52 agreed to transplantation with a viremic donor heart, as determined by nucleic acid testing (NAT). Participants received whichever heart became available first, either HCV-negative or HCV-positive.

The pre-emptive oral glecaprevir-pibrentasvir regimen began before surgery and was followed by an 8-week course afterwards. Those receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA started glecaprevir-pibrentasvir only when they developed viremia. Patients were followed from enrollment to 1 year after transplantation. Results were compared with 107 historical controls who received HCV-negative hearts during the period of 2014-2018. Across all groups, about 70% of recipients were male and the median age was about 56.

In the cohort, 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT+, five NAT–), with three undergoing simultaneous heart-kidney transplantation. An additional 19 were transplanted with HCV-negative hearts.

All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression, with a median time to clearance of 3.5 days (IQR 0.0-8·3). All 20 achieved SVR 12 weeks after treatment completion. No viremia developed in the five patients receiving NAT-negative hearts. No patients required cessation of DAA therapy and no treatment- or HCV-related adverse event occurred during the study period.

While four of 19 patients who received an HCV-negative heart died, no deaths occurred among the 25 patients in the HCV-positive heart transplant group, and graft survival in this group was also 100% at median follow-up of 10.7 months (range 6.5-18.0).

51成人动漫 recently reported similar positive results from a small study of patients receiving heart/lung transplants with organs from HCV-positive donors.

Comparing cardiac transplant wait times at the center over the past 4 years, Chung and colleagues found a significant reduction in time to transplant for patients willing to accept an organ from an HCV-positive donor. Median pre-transplant waiting times following enrollment in the HCV-positive group were 20 days (IQR 8-57) in those receiving HCV-positive hearts and 48 days (IQR 3-175) in those getting HCV-negative organs. In comparison, historical controls waited a median 101 days for transplants (IQR 2-2,210).

Interpretation

The authors warned, however, that while HCV-positive organ transplants could reduce time to transplantation and waitlist-associated mortality, they could also increase complications related to HCV allograft infection if timely access to effective treatment is not available. At present, health insurance coverage and reimbursements for donor-derived HCV infection are limited by the current environment, which allows payers to deny coverage, subject care providers to lengthy appeals processes, and place the burden of DAA cost on individual patients or transplant centers. "If allograft HCV infection can be pre-emptively treated and uniformly cured with DAA therapy, as we have shown, then we believe it is time to revisit HCV-positive organ allocation policies, acknowledging that a pre-emptive approach will only be successful if DAA therapy can be made routinely available," they wrote.

In an accompanying , Didier Samuel, MD, PhD, of INSERM and the Université Paris-Sud Research Unit 1193 in Villejuif, France, agreed that HCV-infected organs might increase access to transplantation for patients on waiting lists, particularly in countries with a high prevalence of HCV-positive donors.

Samuel cited several caveats, however. First, transplant recipients receive many medications and drug-drug interactions need to be prevented. Second, the use of DAAs substantially increases transplantation costs. In addition, recipients of HCV-positive organs must give informed consent, and rates of SVR seem to be equally high whether DAAs are started before or immediately after transplantation with 4 or 8 weeks of pre-emptive therapy. Finally, HCV infection is rapid and requires pre-emptive DAA therapy to avoid liver disease, and since multiple viral strains are involved, the emergence of resistance is possible and regimens will require expert modification.

"Transplant teams using HCV-positive organs should not be too confident and should have expert virological support, identify the viral strains involved, and ensure that all recipients achieve full SVR," Samuel wrote.

Among study limitations, the authors noted its single-center setting and small sample size. In addition, the short follow-up period precluded assessment of chronic rejection, coronary allograft vasculopathy, and long-term outcomes, including mortality, and further follow-up is required. (Data analysis for the current publication reflects follow-up through May 2019; final study completion is planned for November 2019.)

Additionally, the absence of blinding and the comparison of outcomes in trial participants to those in historical controls made the results subject to selection and performance bias. In addition, the superior early survival results shown in those patients undergoing HCV-positive heart transplantation might be partly attributable to the characteristics of overdose-death donors, including young age and few comorbidities.