Data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found that combination therapy with direct-acting antivirals (DAAs) and ezetimibe─ a cholesterol medication that has also been shown to block the entry of hepatitis C (or HCV) into the bloodstream of uninfected people ─ given immediately before and seven days after transplantation with an organ from a donor infected with HCV entirely prevented or rapidly cured HCV in the recipient.
This short-course treatment strategy reduces costs related to DAAs and allows transplant patients to complete HCV therapy before they are discharged from the hospital, the study's co-authors concluded.
Many potential organ donors are infected with HCV, which can lead to their organs being rejected for transplantation. However, multiple small studies have shown that recipients of HCV-infected organs can be successfully treated after transplantation with DAAs.
This study, conducted by researchers at the Toronto Centre for Liver Disease, University Health Network and the University of Toronto in Ontario, Canada, aimed to evaluate pre-emptive DAA therapy combined with ezetimibe, followed by one week of therapy to either prevent or rapidly clear the infection.
We had done a previous trial treating HCV after transplant. It was generally effective, but there were some challenges.
There were some drug interactions, and we had two patients relapse after a full course of therapy. We thought that if we could prevent transmission, we could avoid all of these problems. By adding an entry inhibitor and preloading the liver with DAAs, we thought that treatment could be significantly shortened and our data support that that is indeed the case."
Jordan Feld, MD, MPH
Feld is the lead author and also the R. Phelan Chair in Translational Liver Disease Research at the University of Toronto and Research Director, Toronto Centre for Liver Disease.
HCV-infected organ donors in the study were considered for lung, heart, kidney or kidney-pancreas transplantation. Organ recipients received glecaprevir/pibrentasvir (300/120 mg) combined with 10 mg of ezetimibe six-to-12 hours before transplantation, then the same therapy daily for seven days orally or by nasogastric tube as required.
For lung transplantation, ex-vivo lung perfusion ─ a procedure to reduce swelling of the lungs while outside of the donor's body during transplantation ─ was used for six hours when clinically indicated. Standard cold preservation was used for other organs.
HCV RNA was tested daily in the patients for 14 days and then weekly for 10 weeks.
13 HCV-negative recipients have received organs from nine HCV-positive donors, including five lung, five kidney, two heart and one kidney-pancreas. The median age of the recipients was 60; 11 were male and 11 were Caucasian. The median donor HCV RNA level was 5.23 log10IU/mL.
Six recipients (46 percent) had detectable but unquantifiable (<15 IU/mL) HCV RNA on the first post-op day, which was undetectable by the second post-op day in five patients and the fourth post-op day in one patient.
Four recipients (31 percent) developed a quantifiable presence of hepatitis C virus in their blood at any point post-transplantation, with a maximum HCV RNA of 2.96 log10IU/mL. However, HCV RNA declined rapidly and was unquantifiable by the fourth post-op day in all four recipients.
All four patients with quantifiable HCV RNA received either kidney (three) or kidney-pancreas (one) transplants, but no other factors were associated with post-transplantation presence of hepatitis C virus in their blood. No relapses were reported with a median 10 weeks of follow-up.
Additionally, one lung transplantation patient died 10 weeks post-op of sepsis, but never had detectable HCV RNA. No other serious adverse events have been reported by patients in the study, and the medications were well tolerated.
"Transplant recipients are understandably nervous about accepting organs from people with HCV infection," says Dr. Feld. "This very short therapy allows them to leave hospital free of HCV, which is a huge benefit. Not only is it cheaper and likely safer, but the patients really prefer not having to worry about HCV with all of the other challenges after a transplant."
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