A seven-day course of direct-acting antiviral treatment started
hours before an organ transplant prevented hepatitis C infection in everyone
who received a transplant from a donor with hepatitis C, researchers from the
Mayo Clinic reported at the International Liver Congress in London this week.
The findings have the potential to increase the number of
people who can receive organ transplants as well as reduce waiting times, the
researchers said.
The opioid overdose epidemic in the United States has led to
an increase in the number of donor organs that are available for transplant –
but also a greater risk that these livers come from donors who had hepatitis C.
Until recently, organs from donors with hepatitis C would be directed to people
with hepatitis C on the transplant waiting list, but the impact of wider
treatment for hepatitis C has led to a decline in end-stage liver disease and a
reduction in the need for liver transplants among people with hepatitis C.
Recipients of an organ from a donor with hepatitis C can
receive direct-acting antiviral treatment after transplantation to cure the
inevitable infection with hepatitis C. This treatment is highly effective, but
it would be preferable if transplant recipients didn’t become infected at all.
Dr Bashar Aqel of the Mayo Clinic College of Medicine,
Phoenix, Arizona told a press conference that the practice of delaying
direct-acting antiviral treatment in transplant recipients until after viremia is
detected is problematic because it may lead to organ rejection or organ fibrosis.
In the United States treatment is often delayed for weeks, if not months, while
patients await insurance company approval to begin direct-acting antiviral treatment.
In 2019, Canadian
researchers reported that 25 patients who received glecaprevir/pibrentasvir
plus ezetimibe for seven days, beginning immediately prior to
transplantation, all avoided becoming infected with hepatitis C.
To test whether direct-acting antiviral drugs could prevent
hepatitis C infection from a donated organ, and whether a shortened regimen
initiated immediately before transplantation was effective, Dr Aqel, and colleagues
recruited 38 people who were in need of solid-organ transplants and had agreed
to receive HCV-positive organs.
Study participants received eight days of treatment with glecaprevir
and pibrentasvir (Maviret), a direct-acting antiviral combination active
against all hepatitis C genotypes and with minimal drug interactions. Of particular
importance, the combination has confirmed safety in people with kidney disease.
Participants also received ezetimibe, a lipid-lowering
agent that blocks hepatitis C entry into liver cells.
The shortened pre-emptive regimen was started 2-4 hours
before the transplant to achieve adequate blood levels and continued for 7 days
after transplantation.
The study recruited 32 kidney transplant recipients, two kidney
and pancreas transplant recipients, three heart transplant recipients and one
heart and kidney transplant recipients. Participants had a median age of 61
years and 63% were males. The median time from transplant listing for HCV viraemic
grafts to transplant was 32, 52, 71, and 151 days for heart, heart/kidney,
kidney, and kidney/pancreas transplant recipients, respectively. The median
donor age was 35 years.
All participants completed the pre-emptive treatment regimen
successfully and none became infected with hepatitis C despite early detection
of HCV RNA between days 1 and 14 in most participants.
The peak viral load, detected on day 1, was 6870 IU/ml but
in most cases transient viremia peaked at lower levels. Twelve had detectable
viremia at day 7 and four at day 14 but all became undetectable by day 21 despite
no further treatment beyond day 7. However,
16% never had detectable viral load.
One kidney transplant recipient died after graft rejection.
In the remaining kidney transplant recipients, kidney function began to
normalise by week 4 and continued to improve through the 24-week follow-up
period.
The shortened regimen saved $36,000 compared to 12 weeks of
post-transplant treatment, said Dr Aqel, and the study findings confirmed that
the shortened regimen is safe and highly effective.