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Combination Therapy Prevents HCV Infection in Non-viremic Organ Recipients
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BOSTON — Hepatitis C infection was prevented or rapidly cured in transplant recipients who received organs from donors infected with the virus following combined treatment with ezetimibe and direct-acting antiviral therapy, according to study results presented at The Liver Meeting 2019.
“Unfortunately, most of you know that the opioid epidemic continues and, with that, an overdose crisis,” Jordan J. Feld, MD, MPH, FAASLD, from the University of Toronto University Health Network, said during a press conference. “What has been observed is that among potential organ donors, particularly those who died of overdose, the prevalence of hepatitis C has increased dramatically.”
During the study period, transplant specialists considered donors infected with HCV for lung, heart, kidney or kidney-pancreas recipients.
To test the possibility of preventing HCV infection, recipients received Mavyret (glecaprevir/pibrentasvir, AbbVie) with ezetimibe 6 hours to 12 hours before transplantation and then daily for 1-week posttransplant.
“Ezetimibe is a cholesterol-lowering drug that is approved and quite safe, but also happens to be a ligand ... for one of the entry factors that hepatitis C uses to enter hepatocytes,” Feld explained.
Of the 13 recipients without HCV who received HCV-infected organs, four developed quantifiable viremia posttransplant with a maximum HCV RNA of 2.96 log 10 IU/mL. HCV RNA declined rapidly and was unquantifiable by day 4 after transplant in all patients.
Six other patients had detectable but unquantifiable HCV RNA at day 1 posttransplant which was undetectable by day 2 in five patients and by day 4 in one patient.
All four patients with quantifiable HCV RNA received kidney or kidney-pancreas transplants, but no other factors correlated with posttransplant viremia. Additionally, Feld reported no relapses to date with a median follow-up of 10.2 weeks (range, 1-12.1 weeks).
Medication was well-tolerated with no serious adverse events related to treatment.
“Despite the horrible tragedy of the opioid epidemic, there is some good to come from the epidemic by using these organs for others,” Feld said. “But we must also focus on what we can do about this epidemic.” – by Talitha Bennett
Reference: Feld JJ. Abstract 0038. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.
Disclosure: Feld reports receiving grant or research support, and serving as a consultant for Abbott, AbbVie, Enanta, Gilead, Janssen, Merck and Roche.
Perspective
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Carlos Romero-Marrero, MD
The proportion of hepatitis C-positive transplant donors has risen significantly with the opioid epidemic and several large series have shown that direct acting antiviral therapy is very effective among HCV-positive transplant recipients, with cure rates near 100%. In the past 2 years, emerging evidence has proven that the use of HCV-positive organs on transplant candidates who do not have HCV infection offers excellent patient and allograft outcomes.
The current posttransplant DAA treatment protocol in our center is to treat these patients for 12 weeks. This adds additional cost to the already high expense of organ transplantation. In this study, Feld and colleagues showed that a short-course therapy with Mavyret (glecaprevir/pibrentasvir, AbbVie) and ezetimibe (acting as an HCV cell entry blocker), given for one dose before transplant and 7 days after transplant, effectively and safely prevented HCV transmission in uninfected organ recipients receiving HCV infected donors.
Importantly, no liver transplant recipients were included in this study and therefore this is applicable for heart, lung, and kidney recipients. If these results are validated in other centers, this preemptive treatment should become the new standard of care to prevent HCV transmission in this patient population. The implementation of this strategy would lower the cost of treating these patients by more than 90% and allow for potential completion of HCV therapy before posttransplant hospital discharge.
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