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Low-level viremia was transiently detectable in 21 recipients in the early post-transplant period, but not after 14 days.
Jordan J. Field, MD
An antiviral regimen could allow hepatitis C virus (HCV) organ donors to safely transplant organs into non-infected recipients.
A team, led by Jordan J. Field, MD, Toronto General Hospital, examined whether antiviral drugs combined with an HCV entry blocker given before and for 7 days following an organ transplant would safety reduce the likelihood of an HCV infection in organ recipients from HCV-infected donors.
Recently, there has been increasing prevalence of potential organ donors with HCV infections, where following transplantation from an infected donor, the establishment of HCV in uninfected recipients is near-universal. This results in the requirement of post-transplant antiviral treatment.
The investigators treated HCV-uninfected organ recipients without pre-existing liver disease with ezetimibe 10 mg and glecaprevir-pibrentasvir 300 or 120 mg prior to and following transplantation from HCV-infected donors no older than 70 without co-infections with HIV, hepatitis B virus, or human T-cell leukemia virus 1 or 2.
Of the 30 participants, 13 received lungs, 10 were transplanted kidneys, 6 received a heart transplant, and 1 individual received a kidney-pancreas from 18 HCV-infected donors. The median age of the patient population was 61, and 23 of the 30 participants were men.
The median donor viral load was 5.11 log 10IU/mL (IQR, 4·55—5·63), with at least 3 HCV genotypes were represented (9 [50%] donors with genotype 1, 2 [11%] with genotype 2, 5 [28%] with genotype 3, and 2 [11%] with unknown genotype).
Each recipient received a single dose 6-12 hours prior to the transplant and once a day for 7 days following the surgery.
The investigators assessed HCV RNA once day for 14 days and once a week for an additional 12 weeks.
The team sought primary endpoints of the prevention of chronic hepatitis C viral infections, as defined by undetectable serum HCV RNA at week 12 following transplant surgery and assessed in the intention-to-treat population.
All 30 participants met the primary endpoint and were HCV RNA negative at the last follow-up (median 36 weeks post-transplant [IQR, 25—47]).
The investigators also found low-level viremia transiently detectable in 21 recipients in the early post-transplant period, but not after 14 days.
The treatment was also well tolerated with no dose reductions or treatment discontinuations and 32 serious adverse events identified in 20 recipients.
The serious adverse events included 1 grade 3 elevation in alanine aminotransferase (ALT) possibly related to treatment and 2 recipient deaths due to causes unrelated to the study drug (sepsis at 49 days and subarachnoid hemorrhage at 109 days post-transplant), with neither patient ever being viremic for HCV.
Non-serious transient elevations in ALT and creatine kinase during the trial dosing period resolved with treatment completion.
“Ezetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors,” the authors wrote. “This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors.”
The study, “Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-center, open-label study,” was published online in The Lancet Gastroenterology & Hepatology.