Clinical Pearls & Morning Reports
Published April 24, 2019
A shortage of available donor hearts and lungs limits transplantation in the United States, where approximately 1000 patients die each year while waiting for these organs. Woolley et al. conducted an open-label pilot trial, which assessed the effect of a preemptive course of direct-acting antiviral treatment early after transplantation on graft survival and clearance of hepatitis C virus (HCV) among uninfected recipients of hearts and lungs obtained from HCV-infected donors. Read the Original Article here.
Q: Has transplantation of organs from HCV-infected donors into uninfected recipients been performed in the past?
A: In the past, transplantation of organs from HCV-infected donors into uninfected recipients typically led to chronic HCV infection in the recipients, with HCV transmission to as many as 82% of the recipients. Some studies have shown an increased mortality from liver disease and the development of accelerated graft damage due to graft vasculopathy among recipients of HCV-infected donor hearts. The development of potent direct-acting antiviral agents to treat HCV infection has provided an opportunity to treat this infection in patients who acquire it through organ transplantation, although the use of organs from infected donors has been controversial.
Q: Which antiviral agents and what duration of therapy might be used for an uninfected recipient of a thoracic organ from an HCV-infected donor?
A: In the trial by Woolley et al., organ recipients received a 4-week regimen of sofosbuvir (at a dose of 400 mg) plus velpatasvir (at a dose of 100 mg) once daily. This regimen was chosen because of its activity against all circulating HCV genotypes and its lack of drug interactions with the immunosuppressive regimens used. It was assumed that the recipients would be exposed to a low hepatitis C viral load at the time of transplantation and initiation of direct-acting antiviral treatment. Therefore, a shorter duration of treatment than that used for patients with chronic HCV infection was hypothesized to be efficacious, since a short regimen is analogous to postexposure prophylaxis.
A: By February 2018, when the stopping boundary for efficacy in the trial by Woolley et al. had been met, 35 patients had been enrolled. The 6-month findings in those 35 patients are presented in their current report. A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation. The median initial viral load was 1800 IU per milliliter (interquartile range, 800 to 6180). The primary outcome — a sustained virologic response 12 weeks after completion of antiviral therapy and graft survival at 6 months — was met in all 35 patients with at least 6 months of follow-up (exact two-sided 95% CI, 90 to 100). All recipients had an undetectable hepatitis C viral load by approximately week 2, and the viral load subsequently remained undetectable. This regimen was effective irrespective of the baseline viral loads. No adverse events or serious adverse events were considered by the investigators and the data and safety monitoring board to be related to trial medication.
A: The trial by Woolley et al. is a small trial; thus, conclusions based on these data should be made with caution. The limitations of this trial include its single-center nature, the small numbers of various HCV genotypes studied, and the limited follow-up time, which does not allow for the long-term assessment of chronic lung-allograft dysfunction or cardiac allograft vasculopathy.