Transplanting kidneys from hepatitis C virus (HCV)-positive donors to HCV-negative recipients (HCV D+/R-) may be successful with prophylactic treatment with direct-acting antivirals (DAAs), according to a study recently published in the Annals of Internal Medicine.
Although kidneys from deceased donors with HCV are increasingly available, hundreds are discarded annually due to the limited number of HCV-viremic candidates. There has been early success with HCV D+/R- kidney transplants by using DAAs, but the optimal timing and duration of this therapy remains unclear. Researchers conducted a single-center, open-label, nonrandomized study investigating a 4-week prophylaxis with a pangenotypic combination of glecaprevir 300 mg and pibrentasvir 120 mg (G/P) (ClinicalTrials.gov identifier: NCT03627299).
Ten subjects from 2018 to 2019 were included and had HCV antibody and RNA negativity; did not have HIV, active hepatitis B virus, or liver disease; and were on the deceased-donor kidney transplant list. Ten donors who were aged 13 to 55 years were also included; they had positive results on HCV nucleic acid testing, no long-term changes on kidney biopsy, and creatinine level below 3.5 mg/dL. Subjects received 1 P/G dose before organ perfusion followed by 1 P/G daily dose for 4 weeks. HCV RNA levels were measured on post-operative days 1 and 4; prophylaxis weeks 1, 2, and 4; and post-prophylaxis follow-up in weeks 1, 4, 8, and 12. The primary efficacy endpoint was proportion of recipients with HCV RNA level below the lower limit of quantification (<15 IU/mL) at follow-up week 12.
The median age at transplant for the recipients and donors was 67 years and 38.5 years, respectively. Females made up 30% and 40% of the recipients and donors, respectively. The primary causes of kidney failure in the recipient group were hypertension (n=4; 40%), polycystic kidney disease (n=2; 20%), glomerulonephritis (n=2; 20%), nephrolithiasis (n=1; 10%), and reflux nephropathy (n=1; 10%).
Results suggest that DAA prophylaxis therapy prevented HCV without treatment-related adverse events or substantial liver enzyme abnormalities. After day 7, HCV RNA was undetectable in all 10 recipients. No treatment-related adverse events of Grade 3 or greater occurred throughout the study. No aminotransferase or bilirubin levels of at least 2.5 the upper limit of normal occurred throughout the study. At follow-up week 12, the median estimated glomerular filtration rate was 54.5 mL/min/1.73 m2. At day 261, one graft failed due to venous thrombosis that was unrelated to HCV or G/P. No episodes of rejection occurred throughout the study.
Limitations of this study include small sample size which may not have identified rare risks such as emergence of resistance.
Overall, the study authors concluded that the, “study provides important proof of concept that HCV D+/R- kidney transplantation with 4-week DAA prophylaxis may prevent HCV infection and shorten wait times.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Durand CM, Barnaba B, Yu S, et al. Four-week direct-acting antiviral prophylaxis for kidney transplantation from hepatitis C-viremic donors to hepatitis C-negative recipients: an open-label nonrandomized study. Published online September 8, 2020. Ann Intern Med. doi:10.7326/M20-1468.