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.

Hepatitis C-Negative Patients Receive Positive Kidney Transplants

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