Two-Week Prophylaxis May Prevent Hep C After Kidney Transplant

Short-term prophylaxis with direct-acting antivirals was fully effective at protecting kidney transplant recipients when their donors had hepatitis C, a proof-of-concept study showed.

In the small, uncontrolled trial, a 2-week prophylactic course prevented hepatitis C infection in all 10 negative recipients of positive donor kidneys, Christine Durand, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues, found.

Only one of these 10 patients had transient liver function abnormalities on labs during the 12 weeks after transplant, the researchers said in an Annals of Internal Medicine brief report.

“Our data shows that if hepatitis C therapy is started before the transplant in order to prevent infection in recipients, the duration can be as short as 2 weeks, rather than 8 or 12 weeks to cure infection,” Durand told MedPage Today. “This means less medications for patients and lower costs for patients and the health system.”

“We believe it is preferable to prevent infection rather than waiting to treat after transmission,” she added, referencing the typical transmit-and-treat approach where direct-acting antivirals are given after transplant. While transmit-and-treat is effective at curing hepatitis C infection, it can lead to some recipients developing donor-specific antibodies, rejection, BK-polyomavirus and cytomegalovirus viremia, and severe fibrosing cholestatic hepatitis C.

The researchers also pointed out that prophylaxis is less costly than a full treatment course. Some prior studies have also evaluated direct-acting antiviral prophylaxis, but it was unclear what the best duration was. This same research group previously achieved 100% efficacy with a 12-week and 4-week course. Other studies looking at a 7-day or shorter course noted transmission rates from 4% through 30%, as well as antiviral resistance.

No rejections and no deaths occurred in the current trial. The median estimated glomerular filtration rate (eGFR) of functioning grafts was 46 mL/min/1.73 m² at week 12, 62 mL/min/1.73 m² at year 1, and 58mL/min/1.73m² at year 2.

The 10 transplant recipients (median age 60) received a dose of glecaprevir 300 mg-pibrentasvir 120 mg (Mavyret) prophylaxis before the kidney transplant, followed by 13 additional once-daily doses after the transplantation. Standard immunosuppression with antithymocyte globulin induction, followed by tacrolimus, mycophenolate mofetil, and prednisone was used.

All recipients were at least 18, had negative hepatitis C RNA results, and did not have HIV or active hepatitis B. All deceased donors were between ages 13 and 60, had positive hepatitis C RNA results, terminal creatinine less than 10 mg/dL (884 μmol/L), and no chronic changes on renal biopsy. Kidney transplants were done at Johns Hopkins from November 2020 to August 2021 and recipients were followed for 2 years.

During prophylaxis week one after transplant, eight of 10 recipients had low-level hepatitis C viremia. At week 12, all had hepatitis C RNA less than the lower limit of quantification — the primary efficacy end point. On postoperative day 5, one recipient who underwent a prior liver transplant developed a grade 3 bilirubin elevation, which resolved by day 9. This recipient also developed liver enzyme elevation on postoperative day 28, which resolved by day 40.

Another recipient had post-kidney transplant eGFR consistently under 10 mL/ min/1.73 m² with graft failure at 4.5 months. A biopsy showed severe tubulointerstitial scarring of uncertain cause, though there was no evidence of hepatitis C-related kidney disease.

“Stay tuned for the results of PREVENT-HCV, a larger study that directly compares this two-week prevention approach to waiting to treat after transmission,” said Durand. The trial is ongoing and estimated to be completed by March 2027.

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