A truncated course of glecaprevir-pibrentasvir (Mavyret) prophylaxis started prior to transplant allowed patients without hepatitis C virus (HCV) infection to safely receive kidneys from HCV-positive donors, a small single-center study found.
In all, 10 transplants from HCV-positive donors to HCV-negative recipients (HCV D+/R-) were performed, and viral RNA was undetectable in all recipients starting at 7 days post-transplant and remained so through 12 weeks of follow-up, reported Niraj Desai, MD, and colleagues from Johns Hopkins University in Baltimore in Annals of Internal Medicine.
All patients received their first dose of the direct-active antiviral (DAA) a few hours before organ perfusion, then one dose daily for 4 weeks, and no treatment-related adverse events or substantial liver enzyme abnormalities were observed during follow-up.
“The dose was absorbed by the liver ahead of the infection, and we observed very low viral loads after transplant,” Desai said. “Our next step is to further shorten the treatment course to 2 weeks.”
Desai told MedPage Today that other studies in this area have used a transmit-and-treat approach, starting antiviral treatment a few days or even a few weeks after transplanting HCV-positive kidneys, which commits the patient to a full 12-week regimen owing to the development of high viral loads.
He noted that upwards of 500 otherwise transplant-viable kidneys are discarded each year in the U.S. because of HCV-positivity and for lack of suitable HCV-positive recipients. Viremic kidneys offer another source of organs and could reduce wait times to transplant, he said.
“This study adds further to the mounting evidence for the safety and efficacy of a prophylactic approach to treatment of HCV in uninfected recipients of HCV-infected donor kidneys,” Raymond Chung, MD, of Massachusetts General Hospital in Boston, told MedPage Today. “They also suggest that a DAA regimen as brief as 4 weeks suffices to prevent allograft infection.”
Chung, who was not involved in the current trial, recently participated in a multicenter 30-patient study of 8 weeks of glecaprevir-pibrentasvir delivered on day 3 after kidney transplantation with excellent results.
“A prophylactic approach begun before the virus has infected the recipient liver could permit truncation of the course of antiviral therapy,” Chung added. “This is an attractive approach, as it minimizes the risk of exposure of the patient to HCV infection.”
The effectiveness of the preemptive approach was confirmed in another recent study of eight HCV D+/R- kidney transplants. And in thoracic grafts, 4 weeks of post-exposure prophylaxis with sofosbuvir/velpatasvir (Epclusa) successfully prevented infection in 44 HCV D+/R- heart and lung transplants.
The open-label study from Desai and colleagues — dubbed REHANNA (Renal Transplants in Hepatitis C Negative Recipients With RNA Positive Donors) — investigated 4-week prophylaxis with the pangenotypic combination of glecaprevir 300 mg and pibrentasvir 120 mg. No DAA treatment was used on the kidney itself.
The transplants were performed in seven men and three women at Johns Hopkins from 2018 to 2019. HCV RNA (lower limit of quantification <15 IU/mL) was measured on postoperative days 1 and 4; at prophylaxis weeks 1, 2, and 4; and at post-prophylaxis follow-up weeks 1, 4, 8, and 12.
The 10 recipients ranged in age from 45 to 75 years (median 67), and seven were white.
As for the 10 donors, they ranged in age from 20 to 45 (median 38.5), and their median HCV RNA level was 377,500 IU/mL (19 to 12,900,000 IU/mL). In terms of HCV genotype, six donors had 1a, one had 1b, two had 3, and one had an undetermined genotype.
No post-transplant deaths occurred during the median 12 months follow-up (range 7.4-12). No recipient experienced grade 3 or higher treatment-related adverse events or aminotransferase or bilirubin levels 2.5 times the upper limit of normal or more at any time point. At week 12, median estimated glomerular filtration rate was 54.5 mL/min/1.73 m2 (30 to 79 mL/min/1.73 m2). One graft failed at day 261 owing to venous thrombosis unrelated to HCV or treatment, but no rejection episodes occurred.
Other researchers have found similar infection cure rates and renal function levels with DAA treatment of recipients receiving kidneys from viremic donors, and prophylactic DAA treatment has also been found to salvage livers from HCV-positive donors that would otherwise have been discarded.
Desai’s group is now planning to test an even shorter treatment course as well as a randomized trial to compare prophylaxis with the transmit-and-treat approach.
The authors acknowledged that the small sample size limited generalizability and may not have identified rare risks such as the emergence of resistance.
Disclosures
Desai reported support from AbbVie and Merck outside the submitted work.
Coauthors reported relationships with Abbvie, GlaxoSmithKline, Gilead, Arbutus, Assembly Biosciences, Biomarin, Immunocore, Janssen, Clinical Care Options, ViralEd, Practice Point, and the National Institutes of Health.
Chung disclosed support from AbbVie, Gilead, and Merck.