Conference Coverage

Short-course DAA therapy may prevent hepatitis transmission in transplant patients



– A short course of direct-acting antiviral therapy combined with ezetimibe prevented or rapidly cured hepatitis C virus infection in transplant recipients receiving organs from infected donors, results of a recent study show.

The regimen, given right before transplantation and for 7 days afterward, reduced the cost of direct-acting antiviral (DAA) therapy and allowed patients to complete hepatitis C virus (HCV) therapy before hospital discharge, according to authors of the study, which was presented at the annual meeting of the American Association for the Study of Liver Diseases.

If confirmed in subsequent studies, this regimen could become the standard of care for donor-positive, recipient-negative transplantation, said lead study author Jordan J. Feld, MD, R. Phelan Chair in translational liver disease research at the University of Toronto and research director at the Toronto Centre for Liver Disease.

“Transplant recipients are understandably nervous about accepting organs from people with HCV infection,” said Dr. Feld in a press release. “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.”

Results of this study come at a time when the proportion of overdose death organ donors is on the rise, from just 1% in 2000 to 15% in 2016, according to Dr. Feld. Overdose deaths account for the largest percentage of HCV-infected donors, most of whom are young and often otherwise healthy, he added.

Recipients of HCV-infected organs can be cured after transplant as a number of studies have previously shown. However, preventing transmission would be better than cure, Dr. Feld said, in part because of issues with drug-drug interactions, potential for relapse, and issues with procuring the drugs after transplant.

Accordingly, Dr. Feld and colleagues sought to evaluate “preemptive” treatment with DAA therapy combined with ezetimibe, which they said has been shown to inhibit HCV entry blockers. The recipients, who were listed for heart, lung, kidney, or kidney-pancreas transplant, were given glecaprevir/pibrentasvir plus ezetimibe starting 6-12 hours prior to transplantation, and then daily for 7 days.

The median age was 36 years for the 16 donors reported, and 61 years for the 25 recipients. Most recipients (12 patients) had a lung transplant, while 8 had a heart transplant, 4 had a kidney transplant, and 1 had a kidney-pancreas transplant.

There were no virologic failures, according to the investigators, with sustained virologic response (SVR) after 6 weeks in 7 patients, and SVR after 12 weeks in the remaining 18. Three recipients did have detectable HCV RNA, though all cleared and had SVR at 6 weeks in one case, and SVR at 12 weeks in the other two, according to the investigators’ report.

Of 22 serious adverse events noted in the study, 1 was considered treatment related, according to the report, and there were 2 deaths among lung transplant patients, caused by sepsis in 1 case to sepsis and subarachnoid hemorrhage in another.

It’s not clear whether ezetimibe is needed in this short-duration regimen, but in any case, it is well tolerated and inexpensive, and so there is “minimal downside” to include it, Dr. Feld and coinvestigators wrote in their report.

Dr. Feld reported disclosures related to Abbvie, Abbott, Enanta Pharmaceuticals, Gilead, Janssen, Merck, and Roche.

SOURCE: Feld JJ et al. The Liver Meeting 2019, Abstract 38.

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