article118

DONATE-HCV

"Transplantation Outcomes in Organ Recipients from Donors with HCV Viremia".The New England Journal of Medicine. 2019.

Clinical Question

Can hearts and lungs transplanted from donors with hepatitis C viremia be safely used in recipients without hepatitis C virus (HCV) infection when a direct-acting antiviral regimen is administered preemptively?

Bottom Line

In patients without HCV infection receiving heart or lung transplants from donors with HCV viremia, a 4-week course of direct-acting antiviral regimen initiated immediately after transplantation prevented the establishment of HCV infection.

Major Points

The shortage of donor organs has prompted investigation into the use of hearts and lungs from donors with HCV viremia, a previously excluded group. This trial studied the preemptive administration of sofosbuvir–velpatasvir immediately after transplantation to block HCV replication, aiming to enable the utilization of such organs and potentially increase the donor pool.

Guidelines

No current guidelines discuss using organs from HCV viremic donors in conjunction with direct-acting antiviral agents for transplantation.

Design

- Open-label trial
- N=44 adult patients (36 lung recipients, 8 heart recipients)
- Intervention: Sofosbuvir–velpatasvir started few hours after transplantation, continued for 4 weeks
- Primary Outcome: Sustained virologic response at 12 weeks post-antiviral therapy and graft survival at 6 months

Population

- Adults with active status on waiting lists for heart or lung transplantation
- Exclusion: Positive for HCV antibodies or HBsAg, creatinine clearance <30 mL/min, or previous graft failure

Interventions

- Recipients received 4-week regimen of sofosbuvir (400 mg) plus velpatasvir (100 mg) daily, starting on the day of transplantation

Outcomes

- Primary Outcome: 100% (35/35) of recipients with 6 months follow-up had no detectable HCV and survived with functioning grafts
- Secondary Outcomes: No treatment-related serious adverse events identified; some cases of acute cellular rejection in lung-transplant recipients
- Other: No irreversible grade 3 or higher adverse events attributed to HCV infection

Criticisms

- Single-center nature of the trial might affect generalizability
- Small number of various HCV genotypes studied
- Short duration of follow-up insufficient for long-term assessment of chronic graft dysfunction or cardiovascular complications

Funding

Partially funded by the Mendez National Institute of Transplantation Foundation, Brigham and Women’s Hospital, and a National Center for Advancing Translational Sciences grant to Harvard Clinical and Translational Science Center.