Meghan E Sise1, David S Goldberg2, Jens J Kort3, Douglas E Schaubel4, Rita R Alloway5, Christine M Durand6, Robert J Fontana7, Robert S Brown8, John J Friedewald9, Stacey Prenner10, J Richard Landis4, Melissa Fernando4, Caitlin C Phillips4, E Steve Woodle11, Adele Rike-Shields11,12, Kenneth E Sherman13, Nahel Elias14, Winfred W Williams1, Jenna L Gustafson15, Niraj M Desai16, Brittany Barnaba6, Silas P Norman17, Mona Doshi17, Samuel T Sultan18, Meredith J Aull18, Josh Levitsky9,19, Dianne S Belshe9, Raymond T Chung20, Peter P Reese4,21. 1. Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 2. Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida. 3. Global Medical Affairs Research and Development, AbbVie Inc., North Chicago, Illinois. 4. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. 5. Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. 6. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. 7. Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, Michigan. 8. Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York. 9. Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 10. Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania. 11. Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio. 12. The Christ Hospital, Cincinnati, Ohio. 13. Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, Ohio. 14. Transplant Center and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. 15. Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts. 16. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. 17. Division of Nephrology, Michigan Medicine, Ann Arbor, Michigan. 18. Division of Transplant Surgery, New York-Presbyterian/Weill Cornell Medicine, New York, New York. 19. Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 20. Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts Chung.Raymond@mgh.harvard.edu. 21. Renal-Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
BACKGROUND: Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable. METHODS: We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function. RESULTS: We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months. CONCLUSIONS: Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.
BACKGROUND: Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable. METHODS: We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function. RESULTS: We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK)viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months. CONCLUSIONS: Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.
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