Short-course treatment prevents hepatitis C after organ transplant

Keith Alcorn
Published:
24 June 2022
Dr Bashar Aqel of the Mayo Institute of Medicine speaking at the International Liver Congress 2022. Photo © Steve Forrest & Andrew McConnell / EASL

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.

Reference

Aqel B et al. Multicenter prospective study for the use of shortened pre-emptive therapy with glecaprevir/pibrentasvir (G/P) and ezetimibe in hepatitis C (HCV) seronegative non-liver solid organ transplant recipients of HCV viremic grafts. International Liver Congress, London, abstract OS002, 2022.