@article{0c27568ae341443a855c8717f14e3a03,
title = "Multicenter study to transplant hepatitis C-infected kidneys (mythic): An open-label study of combined glecaprevir and pibrentasvir to treat recipients of transplanted kidneys from deceased donors with hepatitis c virus infection",
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.",
author = "Sise, {Meghan E.} and Goldberg, {David S.} and Kort, {Jens J.} and Schaubel, {Douglas E.} and Alloway, {Rita R.} and Durand, {Christine M.} and Fontana, {Robert J.} and Brown, {Robert S.} and Friedewald, {John J.} and Stacey Prenner and {Richard Landis}, J. and Melissa Fernando and Phillips, {Caitlin C.} and {Steve Woodle}, E. and Adele Rike-Shields and Sherman, {Kenneth E.} and Nahel Elias and Williams, {Winfred W.} and Gustafson, {Jenna L.} and Desai, {Niraj M.} and Brittany Barnaba and Norman, {Silas P.} and Mona Doshi and Sultan, {Samuel T.} and Aull, {Meredith J.} and Josh Levitsky and Belshe, {Dianne S.} and Chung, {Raymond T.} and Reese, {Peter P.}",
note = "Funding Information: Dr. Peter P. Reese reports receiving grants from Merck for investigator-initiated research into transplant using HCV-infected organs and personal fees from the American Journal of Kidney Diseases/National Kidney Foundation for work as associate editor, outside the submitted work. Dr. David S. Goldberg reports receiving grants from Gilead, and Merck, outside the submitted work. Dr. Meghan E. Sise reports receiving personal fees and grant support to Massachusetts General Hospital from AbbVie, Gilead Sciences, and Merck, outside the submitted work. Dr. Rita Alloway reports receiving research grants from Bristol Myers Squibb (BMS), Hookipa Biotech GMBH, and Novartis, outside the submitted work. Dr. Christine M. Durand reports receiving funding from Gilead Sciences AbbVie, ViiV, and GlaxoSmithKline, outside the submitted work. Dr. Robert J. Fontana reports receiving grants from Gilead, AbbVie, and BMS, outside the submitted work. Dr. Robert Brown Jr. reports receiving grant support to Weill Cornell Medicine from AbbVie, Gilead, and Merck. Dr. Kenneth E. Sherman reports receiving grants from AbbVie, Merck, Gilead, Inovio, Intercept, and BMS; and personal fees from MedPace, Watermark, and Inovio, outside the submitted work. Dr. Raymond T. Chung reports receiving grants to Massachusetts General Hospital from Gilead, AbbVie, Merck, BMS, Janssen, Roche, and Boehringer, outside the submitted work. Dr. Robert S. Brown reports receiving grants and personal fees from AbbVie and Gilead, outside the submitted work. Dr. Niraj M. Desai reports receiving grants and personal fees from Merck and Viacyte, outside the submitted work. Dr. Josh Levitsky reports receiving personal fees from Gilead, outside the submitted work. Dr. John Friedewald reports receiving grant support from AbbVie, Eurofins-Viracor, Hansa, Veloxis, Viela Biopharma, and Vitaeris. Funding Information: The authors would like to acknowledge other research support: M. Sise was supported by National Institutes of Health (NIH) grant K23 DK117014. R. Chung was supported by NIH grant K24 DK078772 and the Massachusetts General Hospital (MGH) Research Scholars Program. AbbVie funded the study and provided G/P through a collaboration study agreement with MGH. MGH was the sponsor of the study. J. Kort reports funding received from AbbVie Inc., during the conduct of the study. R. Chung, D. Goldberg, and M. Sise report grants from AbbVie, during the course of the study. P. Reese, D. Goldberg, C. Durand, R. Fontana, J. Landis, M. Fernando, R. Brown, K. Sherman, R. Alloway, and J. Friedewald report grants from MGH via subcontracts to their respective institutions, to support study activities, during the conduct of the study. Publisher Copyright: Copyright {\textcopyright} 2020 by the American Society of Nephrology",
year = "2020",
month = nov,
doi = "10.1681/ASN.2020050686",
language = "English (US)",
volume = "31",
pages = "2678--2687",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "11",
}