@article{77007339827444fa839f4851a7e95d31,
title = "One-Year Outcomes of the Multi-Center StudY to Transplant Hepatitis C-InfeCted kidneys (MYTHIC) Trial",
abstract = "Introduction: Transplanting kidneys from hepatitis C virus (HCV) viremic donors into HCV-negative patients (HCV D-RNA-positive/R-negative) has evolved from experimental to “standard-of-care” at many centers. Nevertheless, most data derive from single centers and provide only short-term follow-up. Methods: The Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC) study was a multicenter (7 sites) trial of HCV D-RNA-positive/R-negative kidney transplantation (KT) followed by 8 weeks of glecaprevir/pibrentasvir (G/P) initiated 2 to 5 days post-KT. Prespecified outcomes included probability of KT (vs. matched waitlist comparators) and 1-year safety outcomes, allograft function, and survival. Results: Among 63 enrolled patients, 1-year cumulative incidence of KT was approximately 3.5-fold greater for the MYTHIC cohort versus 2055 matched United Network for Organ Sharing (UNOS) comparators who did not opt-in to receive a kidney from an HCV-viremic donor (68% vs. 19%, P < 0.0001). Of 30 HCV D-RNA-positive/R-negative KT recipients, all achieved HCV cure. None developed clinically significant liver disease or HCV-related kidney injury. Furthermore, 1-year survival was 93% and 1-year graft function was excellent (median creatinine 1.17; interquartile range [IQR]: 1.02–1.38 mg/dl). There were 4 cases of cytomegalovirus (CMV) disease among 10 CMV-negative patients transplanted with a kidney from an HCV-viremic/CMV-positive donor. Conclusion: The 1-year findings from this multicenter trial suggest that opting-in for HCV-viremic KT offers can increase probability of KT with excellent 1-year outcomes. Trial Registration: NCT03781726",
keywords = "cytomegalovirus infection, direct-acting antivirals, glecaprevir/pibrentasvir, hepatitis C virus, kidney transplantation, organ allocation",
author = "Sise, {Meghan Elizabeth} and Goldberg, {David Seth} and Schaubel, {Douglas Earl} and Fontana, {Robert J.} and Kort, {Jens J.} and Alloway, {Rita R.} and Durand, {Christine M.} and Blumberg, {Emily A.} and Woodle, {E. Steve} and Sherman, {Kenneth E.} and Brown, {Robert S.} and Friedewald, {John J.} and Desai, {Niraj M.} and Sultan, {Samuel T.} and Josh Levitsky and Lee, {Meghan D.} and Strohbehn, {Ian A.} and Landis, {J. Richard} and Melissa Fernando and Gustafson, {Jenna L.} and Chung, {Raymond T.} and Reese, {Peter Philip}",
note = "Funding Information: This work was supported in part by Health Resources and Services Administration contract HHSH250-2019-00001C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Some data reported here have been supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the OPTN or the U.S. Government. Funding Information: Some of the authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. CMD reports receiving grant support from AbbVie, GlaxoSmithKline, and ViiV and serving on a grant review committee for Gilead Sciences. ND reports being an investigator on clinical trials funded by Merck and a consultant and a speaker for Merck. JL reports conducting research and serving as a speaker and a consultant for Novartis; serving as a consultant and stockholder for Transplant Genomics Inc.; and serving as a speaker for Gilead. JF reports having equity and serving as consultant for Transplant Genomics, Inc.; serving in the consulting and speaker{\textquoteright}s bureau for Novartis; serving in the speaker's bureau for Sanofi; and receiving grant support from Veloxis, AbbVie, Vitaeris, Hansa, Viela Biopharma, and Eurofins–Viracor. JJK is an employee of AbbVie and may hold AbbVie stocks. KES reports receiving research grants/contracts (paid to institution) from AbbVie, Bristol-Myers Squibb, Gilead, Inovio, Intercept, and Merck and serving on the advisory board/consulting for Inovio, UniQure, and Abbott Labs. DSMB reports receiving support from MedPace, Inovio, and Watermark. MES reports receiving grant support to Massachusetts General Hospital from Gilead Sciences, AbbVie, Merck & Co., and EMD Serono; participating in scientific advisory board meetings for Gilead and Travere Therapeutics; and serving as a scientific consultant to Bioporto. PPR reports receiving investigator-initiated grants to the University of Pennsylvania from Merck and Gilead for trials involving HCV-viremic organs. RJF reports receiving grant support from Gilead and AbbVie and providing consulting to Sanofi. RRA reports receiving research grants from Bristol-Myers Squibb, Hookipa Biotech GMBH, and Novartis. RRA is an advisor and on the speakers bureau for Genzyme/Sanofi and Veloxis. RSB reports receiving grant support to Weill Cornell Medicine from Gilead Sciences, AbbVie, and Merck & Co., and having consulted personally for AbbVie, Gilead, and Merck & Co. RTC reports receiving research grant support to Massachusetts General Hospital from AbbVie, Gilead, Merck, Bristol-Myers Squibb, Janssen, Boehringer, and Roche. All the other authors declared no competing interests. Funding Information: The authors acknowledge other research support: MES was supported by NIH K23 DK117014. RTC was supported by NIH K24 DK078772 and the MGH Research Scholars Program. DES was supported in part by NIH R01 DK070869. Funding Information: The authors acknowledge the patients who participated in this study, the exceptional efforts of the Clinical Research Computing Unit at the University of Pennsylvania in their role as data coordinating center and Marie Durborow, in particular, for assistance with this trial; the transplant clinicians and staff at every site for patient care; Drs. Gregory Malat and Jennifer Trofe-Clark for questions related to medication administration. The authors acknowledge other research support: MES was supported by NIH K23 DK117014. RTC was supported by NIH K24 DK078772 and the MGH Research Scholars Program. DES was supported in part by NIH R01 DK070869. This work was supported in part by Health Resources and Services Administration contract HHSH250-2019-00001C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Some data reported here have been supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the OPTN or the U.S. Government. AbbVie funded the study and provided G/P through a collaboration study agreement with the Massachusetts General Hospital. The Massachusetts General Hospital was the sponsor of the study. The investigators had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The investigators confirm the originality of the data and manuscript. MES, DSG, RRA, CD, RJF, RSB, JF, ESW, KES, JL, JDL, JJK, RTC, and PPR designed the study. MES, DSG, RRA, CD, RJF, RSB, JF, ESW, KES, JLG, ND, ML, IAS, SS, JL, RTC, and PPR enrolled and followed the patients. EB adjudicated cases of CMV. DES, MES, DSG, MF, RL, RTC, and PPR analyzed the data. DES, MF, DSG, and PPR made the figures. PPR, MES, DSG, RJF, DES, RTC, and RF drafted the paper. All authors revised the paper and approved the final version of the manuscript. Publisher Copyright: {\textcopyright} 2021 International Society of Nephrology",
year = "2022",
month = feb,
doi = "10.1016/j.ekir.2021.11.022",
language = "English (US)",
volume = "7",
pages = "241--250",
journal = "Kidney International Reports",
issn = "2468-0249",
number = "2",
}
